| 1. |
- Borg, Jörgen, et al.
(författare)
-
Amino-terminal anchored surface display in insect cells and budded baculovirus using the amino-terminal end of neuraminidase.
- 2004
-
Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 114:1-2, s. 21-30
-
Tidskriftsartikel (refereegranskat)abstract
- Methods currently used for surface display on insect cells and budded baculovirus, all utilize the sequences from class I transmembrane proteins. This gives rise to some problems when handling unknown genes or cDNAs encoding full-length proteins. First, the stop codon from the cloned gene will be located upstream of the sequence for the transmembrane region. Second, the chance of getting the sequences encoding the signal peptide and the transmembrane region in frame with the cloned gene is small. To minimize these problems, we here present a method by which cDNAs or genes of interest can be cloned and fused to the codons for the signal peptide and transmembrane region of neuraminidase (NA), a class II transmembrane protein of the influenza virus. By placing both the signal peptide and transmembrane region at the amino-terminal, potential problems regarding stop codons are eliminated and errors in frame-shift minimized. To obtain proof of principle, the gene encoding enhanced green fluorescent protein, EGFP, was subcloned into a shuttle vector downstream of the neuraminidase sequence and the fusion product was then transferred to a baculovirus vector and transfected into insect cells (Sf9). Using this method, EGFP was found to be expressed on the surface of both infected cells and budded virus in an accessible manner.
|
|
| 2. |
- Borg, Jörgen, et al.
(författare)
-
Perilipin is present in islets of Langerhans and protects against lipotoxicity when overexpressed in the beta-cell line INS-1.
- 2009
-
Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 150:7, s. 3049-3057
-
Tidskriftsartikel (refereegranskat)abstract
- Lipids have been shown to play a dual role in pancreatic beta-cells - a lipid-derived signal appears to be necessary for glucose-stimulated insulin secretion, whereas lipid accumulation causes impaired insulin secretion and apoptosis. The ability of the protein perilipin to regulate lipolysis prompted an investigation of the presence of perilipin in the islets of Langerhans. In this study evidence is presented for perilipin expression in rat, mouse and human islets of Langerhans as well as in the rat clonal beta-cell line INS-1. In rat and mouse islets, perilipin was verified to be present in beta-cells. In order to examine if the development of lipotoxicity could be prevented by manipulating the conditions for lipid storage in the beta-cell, INS-1 cells with adenoviral-mediated overexpression of perilipin were exposed to lipotoxic conditions for 72 hours. In cells exposed to palmitate, perilipin overexpression caused increased accumulation of triacylglycerols and decreased lipolysis compared to control cells. Whereas glucose-stimulated insulin secretion was retained following palmitate exposure in cells overexpressing perilipin, it was completely abolished in control beta-cells. Thus, overexpression of perilipin appears to confer protection against the development of beta-cell dysfunction following prolonged exposure to palmitate by promoting lipid storage and limiting lipolysis.
|
|
| 3. |
- Fernandez, Celine, et al.
(författare)
-
Hormone-sensitive lipase is necessary for normal mobilization of lipids during sub-maximal exercise.
- 2008
-
Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 295, s. 179-186
-
Tidskriftsartikel (refereegranskat)abstract
- For the working muscle there are a number of fuels available for oxidative metabolism, including glycogen, glucose and non-esterified fatty acids. Non-esterified fatty acids originate from lipolysis in white adipose tissue, from hydrolysis of VLDL-triglycerides or from hydrolysis of intramyocellular triglyceride stores. A key enzyme in the mobilization of fatty acids from intracellular lipid stores is hormone-sensitive lipase (HSL). The aim of the present study was to investigate the metabolic response of HSL-null mice challenged with exercise or fasting and to examine if other lipases are able to fully compensate for the lack of HSL. The results showed that HSL-null mice have reduced capacity to perform aerobic exercise. The liver glycogen stores were more rapidly depleted in HSL-null mice during treadmill exercise and HSL-null mice had reduced plasma concentrations of both glycerol and non-esterified fatty acids after exercise and fasting, respectively. The data support the hypothesis that in the absence of HSL mice are not able to respond to an exercise challenge with increased mobilization of the lipid stores. Consequently, the impact of the lipid sparing effect on liver glycogen will be reduced in the HSL-null mice, resulting in faster depletion of this energy source, contributing to the decreased endurance during sub-maximal exercise. Key words: Treadmill exercise, lipid metabolism, glycogen, skeletal muscle, liver.
|
|
| 4. |
|
|
| 5. |
- Krintel, Christian, et al.
(författare)
-
Quarternary structure and enzymological properties of the different hormone-sensitive lipase (HSL) isoforms.
- 2010
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:6
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of energy in the form of fatty acids from intracellular stores of neutral lipids. The enzyme has been shown to exist in different isoforms with different molecular masses (84 kDa, 89 kDa and 117 kDa) expressed in a tissue-dependent manner, where the predominant 84 kDa form in adipocytes is the most extensively studied. METHODOLOGY/PRINCIPAL FINDINGS: In this study we employed negative stain electron microscopy (EM) to analyze the quarternary structure of the different HSL isoforms. The results show that all three isoforms adopt a head-to-head homodimeric organization, where each monomer contains two structural domains. We also used enzymatic assays to show that despite the variation in the size of the N-terminal domain all three isoforms exhibit similar enzymological properties with regard to psychrotolerance and protein kinase A (PKA)-mediated phosphorylation and activation. CONCLUSIONS/SIGNIFICANCE: We present the first data on the quaternary structure and domain organization of the three HSL isoforms. We conclude that despite large differences in the size of the N-terminal, non-catalytic domain all three HSL isoforms exhibit the same three-dimensional architecture. Furthermore, the three HSL isoforms are very similar with regard to two unique enzymological characteristics of HSL, i.e., cold adaptation and PKA-mediated activation.
|
|
| 6. |
- Mulder, Hindrik, et al.
(författare)
-
Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact.
- 2003
-
Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 278:38, s. 36380-36388
-
Tidskriftsartikel (refereegranskat)abstract
- Lipid metabolism plays an important role in glucose homeostasis under normal and pathological conditions. In adipocytes, skeletal muscle, and pancreatic beta-cells, lipids are mobilized from acylglycerides by the hormone-sensitive lipase (HSL). Here, the consequences of a targeted disruption of the HSL gene for glucose homeostasis were examined. HSL null mice were slightly hyperglycemic in the fasted, but not fed state, which was accompanied by moderate hyperinsulinemia. During glucose challenges, however, disposal of the sugar was not affected in HSL null mice, presumably because of release of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance. Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia.
|
|
| 7. |
- Skoug, Cecilia, et al.
(författare)
-
Genetic deletion of hormone-sensitive lipase in mice reduces cerebral blood flow but does not aggravate the impact of diet-induced obesity on memory
-
Ingår i: Journal of Neurochemistry. - 0022-3042.
-
Tidskriftsartikel (refereegranskat)abstract
- Hormone-sensitive lipase (HSL) is active throughout the brain and its genetic ablation impacts brain function. Its activity in the brain was proposed to regulate bioactive lipid availability, namely eicosanoids that are inflammatory mediators and regulate cerebral blood flow (CBF). We aimed at testing whether HSL deletion increases susceptibility to neuroinflammation and impaired brain perfusion upon diet-induced obesity. HSL−/−, HSL+/−, and HSL+/+ mice of either sex were fed high-fat diet (HFD) or control diet for 8 weeks, and then assessed in behavior tests (object recognition, open field, and elevated plus maze), metabolic tests (insulin and glucose tolerance tests and indirect calorimetry in metabolic cages), and CBF determination by arterial spin labeling (ASL) magnetic resonance imaging (MRI). Immunofluorescence microscopy was used to determine coverage of blood vessels, and morphology of astrocytes and microglia in brain slices. HSL deletion reduced CBF, most prominently in cortex and hippocampus, while HFD feeding only lowered CBF in the hippocampus of wild-type mice. CBF was positively correlated with lectin-stained vessel density. HSL deletion did not exacerbate HFD-induced microgliosis in the hippocampus and hypothalamus. HSL−/− mice showed preserved memory performance when compared to wild-type mice, and HSL deletion did not significantly aggravate HFD-induced memory impairment in object recognition tests. In contrast, HSL deletion conferred protection against HFD-induced obesity, glucose intolerance, and insulin resistance. Altogether, this study points to distinct roles of HSL in periphery and brain during diet-induced obesity. While HSL−/− mice were protected against metabolic syndrome development, HSL deletion reduced brain perfusion without leading to aggravated HFD-induced neuroinflammation and memory dysfunction.
|
|
| 8. |
- Skoug, Cecilia, et al.
(författare)
-
Hormone-sensitive lipase is localized at synapses and is necessary for normal memory functioning in mice
- 2022
-
Ingår i: Journal of Lipid Research. - : Elsevier BV. - 1539-7262 .- 0022-2275. ; 63:5
-
Tidskriftsartikel (refereegranskat)abstract
- Hormone-sensitive lipase (HSL) is mainly present in adipose tissue where it hydrolyses diacylglycerol. Although expression of HSL has also been reported in the brain, its presence in different cellular compartments is uncertain, and its role in regulating brain lipid metabolism remains hitherto unexplored. We hypothesized HSL might play a role in regulating the availability of bioactive lipids necessary for neuronal function, and therefore investigated whether dampening HSL activity could lead to brain dysfunction. In mice, we found HSL protein and enzymatic activity throughout the brain, both localized within neurons and enriched in synapses. HSL-null mice were then analyzed using a battery of behavioral tests. Relative to wild-type littermates, HSL-null mice showed impaired short- and long-term memory, yet preserved exploratory behaviurs. Molecular analysis of the cortex and hippocampus showed increased expression of genes involved in glucose utilization in the hippocampus, but not cortex, of HSL-null mice compared to controls. Furthermore, lipidomics analyses indicated an impact of HSL deletion on the profile of bioactive lipids, including a decrease in endocannabinoids and eicosanoids that are known to modulate neuronal activity, cerebral blood flow, and inflammation processes. Accordingly, mild increases in the expression of pro-inflammatory cytokines in HSL mice compared to littermates were suggestive of low-grade inflammation. We conclude that HSL has a homeostatic role in maintaining pools of lipids required for normal brain function. It remains to be tested, however, whether the recruitment of HSL for the synthesis of these lipids occurs during increased neuronal activity, or whether HSL participates in neuroinflammatory responses.
|
|
| 9. |
- Ström, Kristoffer, et al.
(författare)
-
Attainment of brown adipocyte features in white adipocytes of hormone-sensitive lipase null mice.
- 2008
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:3
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hormone-sensitive lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored tri- and diglycerides, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. METHODOLOGY/PRINCIPAL FINDINGS: Following a high-fat diet (HFD) regimen, energy expenditure, measured using indirect calorimetry, was increased in HSL null mice. White adipose tissue of HSL null mice was characterized by reduced mass and reduced protein expression of PPARgamma, a key transcription factor in adipogenesis, and stearoyl-CoA desaturase 1, the expression of which is known to be positively correlated to the differentiation state of the adipocyte. The protein expression of uncoupling protein-1 (UCP-1), the highly specific marker of brown adipocytes, was increased 7-fold in white adipose tissue of HSL null mice compared to wildtype littermates. Transmission electron microscopy revealed an increase in the size of mitochondria of white adipocytes of HSL null mice. The mRNA expression of pRb and RIP140 was decreased in isolated white adipocytes, while the expression of UCP-1 and CPT1 was increased in HSL null mice compared to wildtype littermates. Basal oxygen consumption was increased almost 3-fold in white adipose tissue of HSL null mice and was accompanied by increased uncoupling activity. CONCLUSIONS: These data suggest that HSL is involved in the determination of white versus brown adipocytes during adipocyte differentiation The exact mechanism(s) underlying this novel role of HSL remains to be elucidated, but it seems clear that HSL is required to sustain normal expression levels of pRb and RIP140, which both promote differentiation into the white, rather than the brown, adipocyte lineage.
|
|
| 10. |
- Alsted, Thomas J., et al.
(författare)
-
Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle
- 2013
-
Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 591:20, s. 5141-5155
-
Tidskriftsartikel (refereegranskat)abstract
- In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro lipase activity data, which may not reflect the in vivo lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibres. To circumvent the problem with this contamination we analysed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (P < 0.001). In response to contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P < 0.05). In vitro TG hydrolase activity data revealed that adipose triglyceride lipase (ATGL) and HSL collectively account for approximate to 98% of the TG hydrolase activity in mouse skeletal muscle, other TG lipases accordingly being of negligible importance for lipolysis of IMTG. The present study is the first to demonstrate that contraction-induced lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal muscle. Furthermore, the results suggest that ATGL is activated and plays a major role in lipolysis of IMTG during muscle contractions.
|
|
| 11. |
- Alvariza, Anette, et al.
(författare)
-
A person-centred approach in nursing: Validity and reliability of the Carer Support Needs Assessment Tool
- 2018
-
Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889 .- 1532-2122. ; 35, s. 1-8
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Carer Support Needs Assessment Tool (CSNAT) was developed for use among family caregivers in palliative care for assessment of their support needs. The purpose of this study was to translate and evaluate the validity and reliability of the CSNAT in a sample of Swedish family caregivers and nurses in a palliative care context. Methods: Data for this validation study was collected during 2016 in the context of palliative home care in two larger Swedish cities. The study was conducted in three stages to reach conceptual, semantic, operational and measurement equivalence between the original UK version and the Swedish version. Stage I consisted of translation to Swedish. In Stage II, cognitive interviews were performed with 8 family caregivers and 10 nurses. Data were analyzed based on relevance, clarity and sensitivity. In Stage III, the CSNAT and related self-rating measures (caregiver burden, preparedness for caregiving and quality of life) were completed by 118 family caregivers. Data quality, construct validity and test-retest reliability were evaluated. Results: The CSNAT items were considered relevant and useful to identify areas of support needs. The Swedish CSNAT showed sound psychometric properties with satisfactory data quality and few problems with missing data across items (1.8%-6.1%). All items except one correlated as expected (rho>0.3) with caregiver burden, supporting construct validity. All items had satisfactory test-retest reliability (κw=0.45-0.75). Conclusions: This study further adds to the validity of the CSNAT and shows in addition that it is reliable and stable for use among family caregivers in palliative care. © 2018 Elsevier Ltd
|
|
| 12. |
- Alvariza, Anette, et al.
(författare)
-
Carer Support Needs and Quality of Life in Palliative Care: A Methodological and Empiri-cal Study
- 2019
-
Ingår i: 16th Word Congress of the European Association for Palliative Care (EAPC). Berlin, May 23-25, Abstract P01-148..
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Carer Support Needs Assessment Tool (CSNAT) was developed to identify support needs of family carers in the context of palliative care which aims to improve quality of life, not just of patients but also their families. Aims: This study aims to 1) evaluate validity and reliability of the CSNAT in a sample of Swedish family carers and nurses in a specialised palliative care context, 2) investigate associations between carer support needs and quality of life. Methods: The study was conducted in four stages I: translation of CSNAT to Swedish; II: cognitive interviews with 8 family carers and 10 nurses; III: completion of the CSNAT, Preparedness for Caregiving Scale, Caregiver Burden Scale, Quality of Life in Life Threatening Illness- Family Carer Version by 118 family carers (spouses/partners: mean age 68 years; 69 women and 45 men). Evaluation of data quality, construct validity and test-retest reliability; IV: Investigation of associations between carer support needs and qual- ity of life using linear regression analyses. Results: CSNAT items were considered relevant and useful to identify support needs and demonstrated sound psychometric properties with satisfactory data quality and few problems with missing data. All items had satisfactory test-retest reliability. Construct validity was supported, as CSNAT items correlated with caregiver burden and preparedness. Associations were found between CSNAT items and seven different domains that represent carer quality of life; carer state, patient wellbe- ing, quality of care, outlook, environment and finances. Having more support needs was associated with poorer quality of life. Conclusion: This study adds to the validity of the CSNAT and shows in addition that it is reliable and stable for use among family carers in pal- liative care. Associations between carer support needs and quality of life suggests that carers’ quality of life may be improved by acknowledging and addressing their needs for support.
|
|
| 13. |
|
|
| 14. |
- Andersson, Kristina E, et al.
(författare)
-
Diverse effects of oats on cholesterol metabolism in C57BL/6 mice correlate with expression of hepatic bile acid-producing enzymes.
- 2013
-
Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 52:7, s. 1755-1769
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We previously reported that two substrains of C57BL/6 mice respond differently to oats with respect to reduction in plasma cholesterol. Analysis of this difference might offer clues to mechanisms behind the cholesterol-lowering effect of oats. Here, we address the possible roles of hepatic steroid metabolism and the intestinal microbiota in this respect. METHODS: Female C57BL/6 mice were fed an atherogenic diet with oat bran (27 %) or control fibres for 4 weeks. RESULTS: C57BL/6 NCrl mice responded to oat bran with 19 ± 1 % (P < 0.001) lower plasma cholesterol, 40 ± 5 % (P < 0.01) higher excretion of bile acids and increased expression of the bile acid-producing hepatic enzymes CYP7A1 and CYP8B1, but none of these effects were found in C57BL/6JBomTac mice. However, on control diet, C57BL/6JBomTac had tenfold higher expression of CYP7A1 and levels of hepatic cholesterol esters than C57BL/6NCrl mice. Plasma levels of fructosamine indicated improved glycemic control by oat bran in C57BL/6NCrl but not in C57BL/6JBomTac. C57BL/6JBomTac had higher intestinal microbiota diversity, but lower numbers of Enterobacteriaceae, Akkermansia and Bacteroides Fragilis than C57BL/6NCrl mice. Oat bran increased bacterial numbers in both substrains. Microbiota diversity was reduced by oats in C57BL/6JBomTac, but unaffected in C57BL/6NCrl. CONCLUSIONS: Our data do not support a connection between altered microbiota diversity and reduced plasma cholesterol, but the bacterial composition in the intestine may influence the effects of added fibres. The cholesterol-lowering properties of oats involve increased production of bile acids via the classical pathway with up-regulation of CYP7A1 and CYP8B1. Altered cholesterol or bile acid metabolism may interfere with the potential of oats to reduce plasma cholesterol.
|
|
| 15. |
- Andersson, Malte, 1941, et al.
(författare)
-
”Minskande befolkning är inte problemet”
- 2020
-
Ingår i: Dagens Nyheter. ; :1 augusti, DN-debatt
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Nätverket Population Matters Sweden: En uppmärksammad studie i The Lancet pekar mot en lägre befolkningsökning i världen än tidigare prognoser. Men en miljard människor till är fortfarande långt över vad jorden klarar. Befolkningstrenden måste snarare vända neråt, och det kräver åtgärder för att stärka kvinnors rättigheter världen över.
|
|
| 16. |
- Anthonsen, M W, et al.
(författare)
-
Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro
- 1998
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 273:1, s. 215-221
-
Tidskriftsartikel (refereegranskat)abstract
- Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in lipolysis. Stimulation of rat adipocytes with isoproterenol results in phosphorylation of HSL and a 50-fold increase in the rate of lipolysis. In this study, we used site-directed mutagenesis and two-dimensional phosphopeptide mapping to show that phosphorylation sites other than the previously identified Ser-563 are phosphorylated in HSL in response to isoproterenol stimulation of 32P-labeled rat adipocytes. Phosphorylation of HSL in adipocytes in response to isoproterenol and in vitro phosphorylation of HSL containing Ser --> Ala mutations in residues 563 and 565 (S563A, S565A) with protein kinase A (PKA), followed by tryptic phosphopeptide mapping resulted in two tryptic phosphopeptides. These tryptic phosphopeptides co-migrated with the phosphopeptides released by the same treatment of F654HPRRSSQGVLHMPLYSSPIVK675 phosphorylated with PKA. Analysis of the phosphorylation site mutants, S659A, S660A, and S659A,S660A disclosed that mutagenesis of both Ser-659 and Ser-660 was necessary to abolish the activation of HSL toward a triolein substrate after phosphorylation with PKA. Mutation of Ser-563 to alanine did not cause significant change of activation compared with wild-type HSL. Hence, our results demonstrate that in addition to the previously identified Ser-563, two other PKA phosphorylation sites, Ser-659 and Ser-660, are present in HSL and, furthermore, that Ser-659 and Ser-660 are the major activity controlling sites in vitro.
|
|
| 17. |
- Anthonsen, Marit W, et al.
(författare)
-
Partial purification and identification of hormone-sensitive lipase from chicken adipose tissue
- 1997
-
Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 236:1, s. 94-99
-
Tidskriftsartikel (refereegranskat)abstract
- HSL from chicken adipose tissue exhibits remarkable activation upon phosphorylation with cAMP-dependent protein kinase (cAMP-PK) compared to HSL from rat and human adipose tissue. In order to characterize the chicken HSL enzyme, it was purified 3500 fold from a chicken adipose tissue homogenate using pH 5.2 precipitation and anion-exchange chromatography. The purified chicken HSL was identified as an 86 kDa protein using Western blot analysis. The HSL diacylglycerol lipase activity was inhibited by 98% upon incubation with anti-rat HSL antiserum, and the specific activity of chicken HSL was estimated to be approximately the same as for the rat enzyme. Furthermore, the 86 kDa polypeptide was phosphorylated by cAMP-PK to about the same stoichiometry as for the recombinant rat enzyme. Hence, our results demonstrate that HSL from chicken adipose tissue is comparable in size and specific activity to HSL from mammalian species, and not a smaller 42 kDa polypeptide with 1000-fold lower specific activity as previously reported.
|
|
| 18. |
|
|
| 19. |
- Axling, Ulrika, et al.
(författare)
-
A low glycaemic diet improves oral glucose tolerance but has no effect on β-cell function in C57BL/6J mice.
- 2010
-
Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 12:11, s. 976-982
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: Clinical studies have suggested a role for dietary glycaemic index (GI) in body weight regulation and diabetes risk. Here, we investigated the long-term metabolic effects of low and high glycaemic diets using the C57BL/6J mouse model. METHODS: Female C57BL/6J mice were fed low or high glycaemic starch in either low-fat or medium-fat diets for 22 weeks. Oral and intravenous glucose tolerance tests were performed to investigate the effect of the experimental diets on glucose tolerance and insulin resistance. RESULTS: In this study, a high glycaemic diet resulted in impaired oral glucose tolerance compared to a low glycaemic diet. This effect was more pronounced in the group fed a medium-fat diet, suggesting that a lower dietary fat content ameliorates the negative effect of a high glycaemic diet. No effect on body weight or body fat content was observed in either a low-fat diet or a medium-fat diet. Static incubation of isolated islets did not show any differences in basal (3.3 mM glucose) or glucose-stimulated (8.6 and 16.7 mM glucose) insulin secretion between mice fed a low or high glycaemic diet. CONCLUSION: Together, our data suggest that the impaired glucose tolerance seen after a high glycaemic diet is not explained by altered β-cell function.
|
|
| 20. |
- Axling, Ulrika, et al.
(författare)
-
Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized, double-blind, cross-over investigation in obese persons.
- 2012
-
Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 66:5, s. 585-590
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES:In studies performed in mice, rose hip powder has been shown to both prevent and reverse high-fat diet-induced obesity and glucose intolerance as well as reduce plasma levels of cholesterol. The aim of this study was to investigate whether daily intake of rose hip powder over 6 weeks exerts beneficial metabolic effects in obese individuals.SUBJECTS/METHODS:A total of 31 obese individuals with normal or impaired glucose tolerance were enrolled in a randomized, double-blind, cross-over study in which metabolic effects of daily intake of a rose hip powder drink over 6 weeks was compared with a control drink. Body weight, glucose tolerance, blood pressure, blood lipids and markers of inflammation were assessed in the subjects.RESULTS:In comparison with the control drink, 6 weeks of daily consumption of the rose hip drink resulted in a significant reduction of systolic blood pressure (-3.4%; P=0.021), total plasma cholesterol (-4.9%; P=0.0018), low-density lipoprotein (LDL) cholesterol (-6.0%; P=0.012) and LDL/HDL ratio (-6.5%; P=0.041). The Reynolds risk assessment score for cardiovascular disease was decreased in the rose hip group compared with the control group (-17%; P=0.007). Body weight, diastolic blood pressure, glucose tolerance, and plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, incretins and markers of inflammation did not differ between the two groups.CONCLUSIONS:Daily consumption of 40 g of rose hip powder for 6 weeks can significantly reduce cardiovascular risk in obese people through lowering of systolic blood pressure and plasma cholesterol levels.European Journal of Clinical Nutrition advance online publication, 14 December 2011; doi:10.1038/ejcn.2011.203.
|
|
| 21. |
- Axling, Ulrika, et al.
(författare)
-
Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice
- 2012
-
Ingår i: Nutrition & Metabolism. - : Springer Science and Business Media LLC. - 1743-7075. ; 9:105
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Type 2 diabetes is associated with obesity, ectopic lipid accumulation and low-grade inflammation. A dysfunctional gut microbiota has been suggested to participate in the pathogenesis of the disease. Green tea is rich in polyphenols and has previously been shown to exert beneficial metabolic effects. Lactobacillus plantarum has the ability to metabolize phenolic acids. The health promoting effect of whole green tea powder as a prebiotic compound has not been thoroughly investigated previously. Methods: C57BL/6J mice were fed a high-fat diet with or without a supplement of 4% green tea powder (GT), and offered drinking water supplemented with Lactobacillus plantarum DSM 15313 (Lp) or the combination of both (Lp + GT) for 22 weeks. Parameters related to obesity, glucose tolerance, lipid metabolism, hepatic steatosis and inflammation were examined. Small intestinal tissue and caecal content were collected for bacterial analysis. Results: Mice in the Lp + GT group had significantly more Lactobacillus and higher diversity of bacteria in the intestine compared to both mice in the control and the GT group. Green tea strongly reduced the body fat content and hepatic triacylglycerol and cholesterol accumulation. The reduction was negatively correlated to the amount of Akkermansia and/or the total amount of bacteria in the small intestine. Markers of inflammation were reduced in the Lp + GT group compared to control. PLS analysis of correlations between the microbiota and the metabolic variables of the individual mice showed that relatively few components of the microbiota had high impact on the correlation model. Conclusions: Green tea powder in combination with a single strain of Lactobacillus plantarum was able to promote growth of Lactobacillus in the intestine and to attenuate high fat diet-induced inflammation. In addition, a component of the microbiota, Akkermansia, correlated negatively with several metabolic parameters known to be risk factors for the development of type 2 diabetes.
|
|
| 22. |
- Axling, Ulrika, et al.
(författare)
-
Increased whole body energy expenditure and protection against diet-induced obesity in Cyp8b1-deficient mice is accompanied by altered adipose tissue features
- 2020
-
Ingår i: Adipocyte. - : TAYLOR & FRANCIS INC. - 2162-3945 .- 2162-397X. ; 9:1, s. 587-599
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to elucidate mechanisms whereby bile acids exert beneficial metabolic effects, using theCyp8b1(-/-)mouse as model. These mice are unable to synthesize cholic acid, resulting in increased synthesis of chenodeoxycholic acid and enlarged bile acid pool.Cyp8b1(-/-)mice were found to be protected against high-fat diet induced obesity. Bomb calorimetry measurements showed increased faecal energy output inCyp8b1(-/)mice. Indirect calorimetry measurements demonstrated increased energy expenditure inCyp8b1(-/-)mice. Meal tolerance tests revealed no differences in glucose disposal, but the insulin response was lower inCyp8b1(-/-)mice. Intravenous glucose tolerance tests, as well as static incubations of isolated islets, showed no difference between the groups, whereas insulin tolerance tests demonstrated improved insulin sensitivity inCyp8b1(-/-)mice. The genes encoding mitochondrial transcription factor A (TFAM) and type 2-iodothyronine deiodinase were upregulated in brown adipose tissue ofCyp8b1(/-)mice and Western blot analyses showed increased abundance of TFAM, and a trend towards increased abundance of UCP1. The upregulation of TFAM and UCP1 was accompanied by increased mitochondrial density, as shown by transmission electron microscopy. White adipocytes ofCyp8b1(-/-)mice exhibited increased responsiveness to both catecholamines and insulin in lipolysis experiments and increased insulin-stimulated lipogenesis. In conclusion, increased energy expenditure, mitochondrial density of brown adipocytes and faecal energy output may all contribute to the protection against diet-induced obesity ofCyp8b1(-/-)mice. Enhanced insulin sensitivity ofCyp8b1(-/-)mice is accompanied by increased hormonal responsiveness of white adipocytes.
|
|
| 23. |
- Axling, Ulrika, et al.
(författare)
-
Metabolic effects of whole grain wheat and whole grain rye in the C57BL/6J mouse.
- 2010
-
Ingår i: Nutrition. - : Elsevier BV. - 1873-1244 .- 0899-9007. ; 26, s. 230-239
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A diet rich in whole grain cereals is suggested to protect against type 2 diabetes and facilitate body weight regulation. However, little is known about the impact of different cereals and the underlying mechanisms. The objective of this study was to compare the long-term metabolic effects of diets supplemented with whole grain wheat or whole grain rye in the C57BL/6J mouse. METHODS: Mice were fed the whole grain supplements in a low-fat background diet for 22 wk. Oral and intravenous glucose tolerance tests were performed during the study and in vitro insulin secretion assays were performed at the end of the study. Body weight, energy intake, body fat content, and plasma parameters were measured during the study. RESULTS: A dietary supplement of whole grain rye suppressed body weight gain and resulted in significantly decreased adiposity, plasma leptin, total plasma cholesterol, and triacylglycerols compared with a supplement of whole grain wheat. Also, a slight improvement in insulin sensitivity was observed in the rye group compared with the wheat group. The decreases in body weight and adiposity were observed in the absence of differences in energy intake. CONCLUSION: Long-term administration of whole grain rye evokes a different metabolic profile compared with whole grain wheat in the C57BL/6J mouse, the primary difference being that whole grain rye reduces body weight and adiposity compared with whole grain wheat. In addition, whole grain rye slightly improves insulin sensitivity and lowers total plasma cholesterol.
|
|
| 24. |
|
|
| 25. |
- Axling, Ulrika, et al.
(författare)
-
Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program
- 2011
-
Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 300:1, s. 111-121
-
Tidskriftsartikel (refereegranskat)abstract
- Andersson U, Henriksson E, Strom K, Alenfall J, Goransson O, Holm C. Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program. Am J Physiol Endocrinol Metab 300: E111-E121, 2011. First published October 19, 2010; doi:10.1152/ajpendo.00268.2010.-The aim of this study was to investigate the metabolic effects of a dietary supplement of powdered rose hip to C57BL/6J mice fed a high-fat diet (HFD). Two different study protocols were used; rose hip was fed together with HFD to lean mice for 20 wk (prevention study) and to obese mice for 10 wk (intervention study). Parameters related to obesity and glucose tolerance were monitored, and livers were examined for lipids and expression of genes and proteins related to lipid metabolism and gluconeogenesis. A supplement of rose hip was capable of both preventing and reversing the increase in body weight and body fat mass imposed by a HFD in the C57BL/6J mouse. Oral and intravenous glucose tolerance tests together with lower basal levels of insulin and glucose showed improved glucose tolerance in mice fed a supplement of rose hip compared with control mice. Hepatic lipid accumulation was reduced in mice fed rose hip compared with control, and the expression of lipogenic proteins was downregulated, whereas AMP-activated protein kinase and other proteins involved in fatty acid oxidation were unaltered. Rose hip intake lowered total plasma cholesterol as well as the low-density lipoprotein-to-high-density lipoprotein ratio via a mechanism not involving altered gene expression of sterol regulatory element-binding protein 2 or 3-hydroxymethylglutaryl-CoA reductase. Taken together, these data show that a dietary supplement of rose hip prevents the development of a diabetic state in the C57BL/6J mouse and that downregulation of the hepatic lipogenic program appears to be at least one mechanism underlying the antidiabetic effect of rose hip.
|
|
| 26. |
- Axling, Ulrika, et al.
(författare)
-
Rye bran alkylresorcinols suppress adipocyte lipolysis and hormone-sensitive lipase activity
- 2011
-
Ingår i: Molecular Nutrition and Food Research. - : Wiley. - 1613-4133 .- 1613-4125. ; 55, s. 290-293
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of alkylresorcinols (ARs) isolated from rye bran on adipocyte lipolysis, hormone-sensitive lipase activity and phosphorylation and on phosphorylation of protein kinase A substrates were studied. Preincubation with ARs for 18 h suppressed catecholamine-stimulated lipolysis in 3T3-L1 adipocytes. Furthermore, phosphorylation of hormone-sensitive lipase (HSL), a key lipase responsible for stimulated lipolysis, and phosphorylation of protein kinase A substrates, were diminished after preincubation with ARs, whereas HSL protein expression was unaltered. ARs were also shown to inhibit HSL activity in an in vitro assay.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Berger, Karin, et al.
(författare)
-
Cereal Byproducts Have Prebiotic Potential in Mice Fed a High-Fat Diet
- 2014
-
Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 62:32, s. 8169-8178
-
Tidskriftsartikel (refereegranskat)abstract
- Barley husks, rye bran, and a fiber residue from oat milk production were processed by heat pretreatment, various separation steps, and treatment with an endoxylanase in order to improve the prebiotic potential of these cereal byproducts. Metabolic functions were intended to improve along with improved microbial activity. The products obtained were included in a high-fat mouse diet so that all diets contained 5% dietary fiber. In addition, high-fat and low-fat controls as well as partially hydrolyzed guar gum were included in the study. The soluble fiber product obtained from rye bran caused a significant increase in the bifidobacteria (log copies of 16S rRNA genes; median (25−75 percentile): 6.38 (6.04−6.66) and 7.47 (7.30−7.74), respectively; p < 0.001) in parallel with a tendency of increased production of propionic acid and indications of improved metabolic function compared with high-fat fed control mice. The oat-derived product caused an increase in the pool of cecal propionic (from 0.62 ± 0.12 to 0.94 ± 0.08) and butyric acid (from 0.38 ± 0.04 to 0.60 ± 0.04) compared with the high-fat control, and it caused a significant increase in lactobacilli (log copies of 16S rRNA genes; median (25−75 percentile): 6.83 (6.65−7.53) and 8.04 (7.86−8.33), respectively; p < 0.01) in the cecal mucosa. However, no changes in measured metabolic parameters were observed by either oat or barley products.
|
|
| 31. |
|
|
| 32. |
- Birgersson, Madeleine, et al.
(författare)
-
Intestinal estrogen receptor beta modulates the tumor immune microenvironment in a mouse model of colitis-associated cancer
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Chronic inflammation promotes the development of colorectal cancer (CRC), as evidenced by patients with inflammatory bowel disease (IBD), and sex disparities are evident in CRC. The tumor microenvironment (TME) is composed of stromal cells and infiltrating immune cells that directly affect processes including antitumor immunity. We have previously shown that intestinal estrogen receptor beta (ERβ) protects against colitis and colitis-induced cancer (CAC) by modulating inflammatory signaling and that males are more sensitive to the induction of colitis and cancer. However, sex differences between tumors and the impact of ERβ the tumor immune microenvironment have not been investigated. In this study, we have analyzed colon samples from AOM/DSS-treated wild-type and ERβKOVil mice (that lack intestinal ERβ) and profiled the differences in the transcriptome and immune response to CAC on the basis of sex and ERβ expression. RNA-sequencing revealed differences in gene expression and enriched biological processes depending on sex and genotype, and the immune response to cancer appears altered between tumors from female WT and ERβKOVil mice. Immunostaining subsequently showed that tumors from ERβKOVil mice display significantly increased CD68+ macrophage infiltration, decreased CD3+ T cell infiltration, and, strikingly, impaired NK cell infiltration. Here, for the first time, we show that intestinal ERβ modulates the tumor immune microenvironment during CAC and that lack of intestinal ERβ appears to promote the formation of an immunosuppressive TME. Our findings indicate that activation of ERβ could be used to treat CRC, possibly together with immunotherapies, and provide a foundation for future studies investigating ERβ and immunity.
|
|
| 33. |
- Bjursten, Henrik, et al.
(författare)
-
Particle separation using ultrasound can radically reduce embolic load to brain after cardiac surgery.
- 2004
-
Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 78:5, s. 1572-1578
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Microembolism during cardiopulmonary bypass has been suggested as being the predominant cause of neurocognitive disorders after cardiac surgery. Shed blood, normally retransfused into the patient during cardiopulmonary bypass, is a major source of lipid microemboli in the brain capillaries. A newly developed technique based on acoustic standing-wave separation of particles in fluid in microchannels, with the capacity to remove lipid particles in blood, is presented. Methods. A separator consisting of eight parallel, high-fidelity microfabricated channels was actuated with an ultrasound field to create a standing wave. Three different concentrations of lipid particles (diameter, 0.3 mum) were added to blood samples with increasing hematocrits and introduced into the separator channels to separate lipid particles and erythrocytes. Results. The mean separation rates for lipid particles were 81.9% +/- 7.6% and for erythrocytes 79.8% +/- 9.9%, and both were related to the hematocrit level of the incoming blood sample. The procedure was atraumatic and did not cause hemolysis. Conclusions. Particle separation by means of an acoustic standing-wave technique can be used for atraumatic and effective removal of lipid particles from blood, with the possible clinical implication of reducing neurocognitive complications after cardiopulmonary bypass. (C) 2004 by The Society of Thoracic Surgeons.
|
|
| 34. |
- Blaise, Régis, et al.
(författare)
-
Testis hormone-sensitive lipase expression in spermatids is governed by a short promoter in transgenic mice
- 2001
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 276:7, s. 5109-5115
-
Tidskriftsartikel (refereegranskat)abstract
- A testicular form of hormone-sensitive lipase (HSLtes), a triacylglycerol lipase, and cholesterol esterase, is expressed in male germ cells. Northern blot analysis showed HSLtes mRNA expression in early spermatids. Immunolocalization of the protein in human and rodent seminiferous tubules indicated that the highest level of expression occurred in elongated spermatids. We have previously shown that 0.5 kilobase pairs of the human HSLtes promoter directs testis-specific expression of a chloramphenicol acetyltransferase reporter gene in transgenic mice and determined regions binding nuclear proteins expressed in testis but not in liver (Blaise, R,, Grober, J,, Rouet, P., Tavernier, G., Daegelen, D., and Langin, D. (1999) J. Biol. Chem. 274, 9327-9334). Mutation of a SRY/Sox-binding site in one of the regions did not impair in vivo testis-specific expression of the reporter gene. Further transgenic analyses established that 95 base pairs upstream of the transcription start site were sufficient for correct testis expression. In gel retardation assays using early spermatid nuclear extracts, a germ cell-specific DNA-protein interaction was mapped between -46 and -29 base pairs. The DNA binding nuclear protein showed properties of zinc finger transcription factors. Mutation of the region abolished reporter gene activity in transgenic mice, showing that it is necessary for testis expression of HSLtes.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Bostrom, E. A., et al.
(författare)
-
Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines
- 2015
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
-
Tidskriftsartikel (refereegranskat)abstract
- Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-alpha (TNF-alpha and interleukin-1 beta (IL-1 beta), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-kappa B pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in periodontitis and maybe prevent tooth loss.
|
|
| 38. |
- Burgess, SC, et al.
(författare)
-
Effect of murine strain on metabolic pathways of glucose production after brief or prolonged fasting
- 2005
-
Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 289:1, s. 53-61
-
Tidskriftsartikel (refereegranskat)abstract
- Background strain is known to influence the way a genetic manipulation affects mouse phenotypes. Despite data that demonstrate variations in the primary phenotype of basic inbred strains of mice, there is limited data available about specific metabolic fluxes in vivo that may be responsible for the differences in strain phenotypes. In this study, a simple stable isotope tracer/NMR spectroscopic protocol has been used to compare metabolic fluxes in ICR, FVB/N (FVB), C57BL/6J (B6), and 129S1/SvImJ (129) mouse strains. After a short-term fast in these mice, there were no detectable differences in the pathway fluxes that contribute to glucose synthesis. However, after a 24-h fast, B6 mice retain some residual glycogenolysis compared with other strains. FVB mice also had a 30% higher in vivo phosphoenolpyruvate carboxykinase flux and total glucose production from the level of the TCA cycle compared with B6 and 129 strains, while total body glucose production in the 129 strain was similar to 30% lower than in either FVB or B6 mice. These data indicate that there are inherent differences in several pathways involving glucose metabolism of inbred strains of mice that may contribute to a phenotype after genetic manipulation in these animals. The techniques used here are amenable to use as a secondary or tertiary tool for studying mouse models with disruptions of intermediary metabolism.
|
|
| 39. |
- Cavalera, Michele, et al.
(författare)
-
Dietary rose hip exerts antiatherosclerotic effects and increases nitric oxide-mediated dilation in ApoE-null mice
- 2017
-
Ingår i: Journal of Nutritional Biochemistry. - : Elsevier BV. - 0955-2863. ; 44, s. 52-59
-
Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is a disease in which atheromatous plaques develop inside arteries, leading to reduced or obstructed blood flow that in turn may cause stroke and heart attack. Rose hip is the fruit of plants of the genus Rosa, belonging to the Rosaceae family, and it is rich in antioxidants with high amounts of ascorbic acid and phenolic compounds. Several studies have shown that fruits, seeds and roots of these plants exert antidiabetic, antiobesity and cholesterol-lowering effects in rodents as well as humans. The aim of this study was to elucidate the mechanisms by which rose hip lowers plasma cholesterol and to evaluate its effects on atherosclerotic plaque formation. ApoE-null mice were fed either an HFD (CTR) or HFD with rose hip supplementation (RH) for 24 weeks. At the end of the study, we found that blood pressure and atherosclerotic plaques, together with oxidized LDL, total cholesterol and fibrinogen levels were markedly reduced in the RH group. Fecal cholesterol content, liver expression of Ldlr and selected reverse cholesterol transport (RCT) genes such as Abca1, Abcg1 and Scarb1 were significantly increased upon RH feeding. In the aorta, the scavenger receptor Cd36 and the proinflammatory Il1β genes were markedly down-regulated compared to the CTR mice. Finally, we found that RH increased nitric oxide-mediated dilation of the caudal artery. Taken together, these results suggest that rose hip is a suitable dietary supplement for preventing atherosclerotic plaques formation by modulating systemic blood pressure and the expression of RCT and inflammatory genes.
|
|
| 40. |
- Cavalera, Michele, et al.
(författare)
-
Rose hip supplementation increases energy expenditure and induces browning of white adipose tissue
- 2016
-
Ingår i: Nutrition & Metabolism. - : Springer Science and Business Media LLC. - 1743-7075. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Overweight and obesity are widespread chronic disorders defined as excessive fat accumulation, and are major risk factors for several chronic diseases including type 2 diabetes, coronary heart disease, high blood pressure and fatty liver. Changes in lifestyle such as increased physical activity and a healthy diet can be crucial tools for treating obesity. Intake of rose hip, the fruit of several plants belonging to the Rosaceae family, has been shown to reduce body fat mass and prevent body weight gain. Thus, the aim of the study was to elucidate potential mechanisms through which rose hip inhibit diet-induced obesity. Methods: C57BL/6 J mice were fed a high fat diet with (RH) or without (CTR) rose hip supplementation for three months. In vivo indirect calorimetry was monitored, as well as gene expression and protein levels of different adipose depots. Results: Although no differences in energy intake were found compared to the CTR group, RH prevented body weight gain and lowered blood glucose, insulin and cholesterol levels. Indirect calorimetry showed that RH-fed mice have significantly higher EE during the dark phase, despite comparable voluntary activity. Moreover, when challenged with treadmill running, RH-fed mice exhibited higher metabolic rate. Therefore, we hypothesized that RH could stimulate the brown adipose tissue (BAT) thermogenic capacity or may induce browning of the white adipose tissue (WAT). Compared to the CTR group, gene expression and protein levels of some brown and "brite"markers, together with genes able to promote brown adipocyte differentiation and thermogenesis (such as ucp1, tbx15, bmp7, and cidea), as well as phosphorylation of AMPK, was increased in WAT (but not in BAT) of RH-fed mice. Conclusions: Taken together these results indicate that dietary rose hip prevents body weight gain by increasing whole body EE and inducing browning of WAT. Thus, it has potential therapeutic implication for treatment of obesity and related metabolic disorders.
|
|
| 41. |
- Do, Ron, et al.
(författare)
-
Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
-
Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
|
|
| 42. |
- Donsmark, M, et al.
(författare)
-
Contractions activate hormone-sensitive lipase in rat muscle by protein kinase C and mitogen-activated protein kinase
- 2003
-
Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 550:3, s. 845-854
-
Tidskriftsartikel (refereegranskat)abstract
- Intramuscular triacylglycerol is an important energy store and is also related to insulin resistance. The mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by both adrenaline and contractions. Adrenaline acts via cAMP-dependent protein kinase (PKA). The signalling mediating the effect of contractions is unknown and was explored in this study. Incubated soleus muscles from 70 g male rats were electrically stimulated to perform repeated tetanic contractions for 5 min. The contraction-induced activation of HSL was abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide I and calphostin C and reduced 50 % by the mitogen-activated protein kinase kinase (MEK) inhibitor U0126, which also completely blocked extracellular signal-regulated kinase (ERK) 1 and 2 phosphorylation. None of the inhibitors reduced adrenaline-induced HSL activation in soleus muscle. Both phorbol-12-myristate-13-acetate (PMA), which activates PKC and, in turn, ERK, and caffeine, which increases intracellular Ca2+ without eliciting contraction, increased HSL activity. Activated ERK increased HSL activity in supernatant from basal but not from electrically stimulated muscle. In conclusion, in muscle, PKC can stimulate HSL through ERK. Contractions and adrenaline enhance muscle HSL activity by different signalling mechanisms. The effect of contractions is mediated by PKC, at least partly via the ERK pathway.
|
|
| 43. |
- Donsmark, M, et al.
(författare)
-
Contractions induce phosphorylation of the AMPK site Ser(565) in hormone-sensitive lipase in muscle
- 2004
-
Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 316:3, s. 867-871
-
Tidskriftsartikel (refereegranskat)abstract
- Intramyocellular triglyceride is an important energy store which is related to insulin resistance. Mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by epinephrine via PKA and by contractions via PKC and ERK. 5' AMP-activated protein kinase (AMPK) is an intracellular fuel gauge which regulates metabolism. In this Study we incubated rat soleus Muscle to investigate if AMPK influences HSL during 5 min of repeated tetanic contractions. An eightfold increase in AMPK activity was accompanied by a 2.5-fold increase in phosphorylation of the AMPK-site Ser(565) in HSL (p < 0.05). Inhibition of PKC by Calphostin C abolished the contraction-mediated HSL activation while HSL-Ser(565) phosphorylation was not reduced. The study indicates that during contractions AMPK phosphorylates HSL in Ser(565), but this phosphorylation is not directly responsible for the contraction-induced activation of HSL.
|
|
| 44. |
- Donsmark, Morten, et al.
(författare)
-
Hormone-Sensitive Lipase as Mediator of Lipolysis in Contracting Skeletal Muscle.
- 2005
-
Ingår i: Exercise and Sport Sciences Reviews. - 1538-3008. ; 33:3, s. 127-133
-
Forskningsöversikt (refereegranskat)abstract
- The authors propose that the enzyme hormone-sensitive lipase (HSL), which is the rate-limiting enzyme for hydrolysis of triacylglycerol in adipocytes, also regulates the intramyocellular triacylglycerol mobilization and is controlled by mechanisms similar to those regulating glycogen phosphorylase. From an exercise perspective, it is fascinating that the primary enzymatic setting allows simultaneous mobilization of all major extramuscular and intramuscular energy stores.
|
|
| 45. |
- Donsmark, M, et al.
(författare)
-
Regulation and role of hormone-sensitive lipase in rat skeletal muscle
- 2004
-
Ingår i: Proceedings of the Nutrition Society. - 0029-6651. ; 63:2, s. 309-314
-
Tidskriftsartikel (refereegranskat)abstract
- Intramyocellular triacylglycerol (TG) is an important energy store, and the energy content of this depot is higher than the energy content of the muscle glycogen depot. It has recently been shown that the mobilization of fatty acids from this TG pool may be regulated by the neutral lipase hormone-sensitive lipase (HSL). This enzyme is known to be rate limiting for intracellular TG hydrolysis in adipose tissue. The presence of HSL has been demonstrated in all muscle fibre types by Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying. The content of HSL varies between fibre types, being higher in oxidative fibres than in glycolytic fibres. When analysed under conditions optimal for HSL, neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions. These increases are abolished by the presence of anti-HSL antibody during analysis. Moreover, immunoprecipitation with affinity-purified anti-HSL antibody causes similar reductions in muscle HSL protein concentration and in measured neutral lipase responses to contractions. The immunoreactive HSL in muscle is stimulated by adrenaline via beta-adrenergic activation of cAMP-dependent protein kinase (PKA). From findings in adipocytes it is likely that PKA phosphorylates HSL at residues Ser(563), Ser(659) and Ser(660). Contraction probably also enhances muscle HSL activity by phosphorylation, because the contraction-induced increase in HSL activity is elevated by the protein phosphatase inhibitor okadaic acid and reversed by alkaline phosphatase. A novel signalling pathway in muscle by which HSL activity may be stimulated by protein kinase C (PKC) via extracellular signal-regulated kinase (ERK) has been demonstrated. In contrast to previous findings in adipocytes, in muscle the activation of ERK is not necessary for stimulation of HSL by adrenaline. However, contraction-induced HSL activation is mediated by PKC, at least partly via the ERK pathway. In fat cells ERK is known to phosphorylate HSL at Ser(600). Hence, phosphorylation of different sites may explain the finding that in muscle the effects of contractions and adrenaline on HSL activity are partially additive. In line with the view that the two stimuli act by different mechanisms, training increases contraction-mediated HSL activation but diminishes adrenaline-mediated HSL activation in muscle. In conclusion, HSL is present in skeletal muscle and can be activated by phosphorylation in response to both adrenaline and muscle contractions. Training increases contraction-mediated HSL activation, but decreases adrenaline-mediated HSL activation in muscle.
|
|
| 46. |
- Ek, I, et al.
(författare)
-
A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance
- 2002
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 51:2, s. 484-492
-
Tidskriftsartikel (refereegranskat)abstract
- The etiology of polycystic ovary syndrome (PCOS) is unknown. However, PCOS has a strong resemblance to the insulin resistance (metabolic) syndrome, where an increased rate of visceral fat cell lipolysis is believed to play a pathophysiological role. We hypothesized that primary defects in visceral lipolysis might also exist in PCOS. Ten young, nonobese, and otherwise healthy PCOS women were compared with 13 matched control women. In vitro lipolysis regulation and stoichiometric properties of the final step in lipolysis activation, namely the protein kinase A (PKA)-hormone sensitive lipase (HSL) complex, were investigated in isolated visceral (i.e., omental) fat cells. Body fat distribution and circulating levels of insulin, glucose, and lipids were normal in PCOS women. However, in vivo insulin sensitivity was slightly decreased (P = 0.03). Catecholamine-induced adipocyte lipolysis was markedly (i.e., about twofold) increased in PCOS women due to changes at the postreceptor level, although there was no change in the antilipolytic properties of visceral fat cells. Western blot analyses of visceral adipose tissue showed twofold increased levels of the catalytic and the regulatory la components of PKA. In contrast, the regulatory RIIbeta component of PKA was almost 50% decreased in visceral adipose tissue in PCOS women. Recent studies on genetically modified mice have shown that a similar transition in the regulatory PKA units induces an increased lipolytic response to catecholamines. Further analysis showed that the level of HSL-short, an enzymatically inactive splice form of HSL, was decreased in PCOS (P < 0.01). The altered lipolysis in PCOS is different from that observed in visceral fat cells in the insulin resistance syndrome that occurs at the level of adrenergic receptors. We concluded that increased catecholamine-induced lipolysis in visceral fat cells may be due to unique alterations in the stoichiometric properties of the adipose PKA-HSL holoenzymes. This could be an early and possibly primary lipolysis defect in PCOS.
|
|
| 47. |
- Enevoldsen, L.H., et al.
(författare)
-
The effect of exercise training on hormone-sensitive lipase in rat intra-abdominal adipose tissue and muscle
- 2001
-
Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 536:3, s. 871-877
-
Tidskriftsartikel (refereegranskat)abstract
- 1. Adrenaline-stimulated lipolysis in adipose tissue may increase with training. The rate-limiting step in adipose tissue lipolysis is catalysed by the enzyme hormone-sensitive lipase (HSL). We studied the effect of exercise training on the activity of the total and the activated form of HSL, referred to as HSL (DG) and HSL (TG), respectively, and on the concentration of HSL protein in retroperitoneal (RE) and mesenteric (ME) adipose tissue, and in the extensor digitorum. longus (EDL) and soleus muscles in rats. 2. Rats (weighing 96 + 1 g, mean +/- S.E.M.) were either swim trained (T, 18 weeks, n = 12) or sedentary (S, n = 12). Then RE and ME adipose tissue and the EDL and soleus muscles were incubated for 20 min with 4.4 muM adrenaline. 3. HSL enzyme activities in adipose tissue were higher in T compared with S rats. Furthermore, in RE adipose tissue, training also doubled HSL protein concentration (P < 0.05). In ME adipose tissue, the HSL protein levels did not differ significantly between T and S rats. In muscle, HSL (TG) activity as well as HSL (TG)/HSL (DG) were. lower in T rats, whereas HSL (DG) activity did not differ between groups. Furthermore, HSL protein concentration in muscle did not differ between T and S rats (P > 0.05). 4. In conclusion, training increased the amount of HSL and the sensitivity of HSL to stimulation by adrenaline in intra-abdominal adipose tissue, the extent of the change differing between anatomical locations. In contrast, in skeletal muscle the amount of HSL was unchanged and its sensitivity to stimulation by adrenaline reduced after training.
|
|
| 48. |
- Enoksson, Staffan, et al.
(författare)
-
Marked Re-Utilization of Free Fatty Acids During Activated Lipolysis in Human Skeletal Muscle.
- 2005
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 90:2, s. 1189-1195
-
Tidskriftsartikel (refereegranskat)abstract
- Release of glycerol and free fatty acids (FFA) was investigated in human skeletal muscle strips. In the basal state, glycerol and FFA were released at almost equimolar rates (0.3 nmol/ng tissue.90 min). A nonselective beta-adrenoceptor agonist, isoprenaline, caused a concentration-dependent stimulation of glycerol release, whereas FFA release was unaffected. Basal and isoprenaline-induced glycerol release correlated positively with the age of the donors (r = 0.5, P < 0.005) but not with their body mass index (P > or = 0.4). Biochemical experiments with hormone-sensitive lipase (HSL) showed that most enzyme activity was both in the cytosol and mitochondrial fraction and that it constituted the common long and active form of the protein. Electron microscopy studies in rat skeletal muscle using labeled highly specific HSL antibodies verified the cytosolic location of HSL and, furthermore, indicated an accumulation of HSL-adjoining mitochondria. These results suggest that FFA produced in myocytes during catecholamine-induced lipolysis are retained by the muscle and, therefore by inference, reused. It is conceivable that efficient hydrolysis of acylglycerol by HSL located in the cytosol as well as near the mitochondria may facilitate mitochondrial FFA oxidation. In addition, muscle lipolysis activity increases during aging and may be independent of total body fat.
|
|
| 49. |
- Fall, Tove, et al.
(författare)
-
The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
- 2013
-
Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
|
|
| 50. |
- Fernandez, Celine, et al.
(författare)
-
Altered Desaturation and Elongation of Fatty Acids in Hormone-Sensitive Lipase Null Mice
- 2011
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Hormone-sensitive lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored lipids, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. The aim of this study was to define lipid profiles in plasma, white adipose tissue (WAT) and liver of HSL null mice, in order to better understand the role of this multifunctional enzyme. Methodology/ Principal Findings: This study used global and targeted lipidomics and expression profiling to reveal changed lipid profiles in WAT, liver and plasma as well as altered expression of desaturases and elongases in WAT and liver of HSL null mice on high fat diet. Decreased mRNA levels of stearoyl-CoA desaturase 1 and 2 in WAT were consistent with a lowered ratio of 16:1n7/16:0 and 18:1n9/18:0 in WAT and plasma. In WAT, increased ratio of 18:0/16:0 could be linked to elevated mRNA levels of the Elovl1 elongase. Conclusions: This study illustrates the importance of HSL for normal lipid metabolism in response to a high fat diet. HSL deficiency greatly influences the expression of elongases and desaturases, resulting in altered lipid profiles in WAT, liver and plasma. Finally, altered proportions of palmitoleate, a recently-suggested lipokine, in tissue and plasma of HSL null mice, could be an important factor mediating and contributing to the changed lipid profile, and possibly also to the decreased insulin sensitivity seen in HSL null mice.
|
|
