| 1. |
- Ahola-Erkkilä, Sofia, et al.
(författare)
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Ketogenic diet slows down mitochondrial myopathy progression in mice
- 2010
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Ingår i: Human Molecular Genetics. - : Elsevier. - 0964-6906 .- 1460-2083. ; 19:10, s. 1974-1984
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction is a major cause of neurodegenerative and neuromuscular diseases of adult age and of multisystem disorders of childhood. However, no effective treatment exists for these progressive disorders. Cell culture studies suggested that ketogenic diet (KD), with low glucose and high fat content, could select against cells or mitochondria with mutant mitochondrial DNA (mtDNA), but proper patient trials are still lacking. We studied here the transgenic Deletor mouse, a disease model for progressive late-onset mitochondrial myopathy, accumulating mtDNA deletions during aging and manifesting subtle progressive respiratory chain (RC) deficiency. We found that these mice have widespread lipidomic and metabolite changes, including abnormal plasma phospholipid and free amino acid levels and ketone body production. We treated these mice with pre-symptomatic long-term and post-symptomatic shorter term KD. The effects of the diet for disease progression were followed by morphological, metabolomic and lipidomic tools. We show here that the diet decreased the amount of cytochrome c oxidase negative muscle fibers, a key feature in mitochondrial RC deficiencies, and prevented completely the formation of the mitochondrial ultrastructural abnormalities in the muscle. Furthermore, most of the metabolic and lipidomic changes were cured by the diet to wild-type levels. The diet did not, however, significantly affect the mtDNA quality or quantity, but rather induced mitochondrial biogenesis and restored liver lipid levels. Our results show that mitochondrial myopathy induces widespread metabolic changes, and that KD can slow down progression of the disease in mice. These results suggest that KD may be useful for mitochondrial late-onset myopathies.
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| 2. |
- Hilvo, Mika, et al.
(författare)
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Monounsaturated fatty acids in serum triacylglycerols are associated with response to neoadjuvant chemotherapy in breast cancer patients
- 2014
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 134:7, s. 1725-1733
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Tidskriftsartikel (refereegranskat)abstract
- Changes in cellular lipid metabolism are a common feature in most solid tumors, which occur already in early stages of the tumor progression. However, it remains unclear if the tumor-specific lipid changes can be detected at the level of systemic lipid metabolism. The objective of this study was to perform comprehensive analysis of lipids in breast cancer patient serum samples. Lipidomic profiling using an established analytical platform was performed in two cohorts of breast cancer patients receiving neoadjuvant chemotherapy. The analyses were performed for 142 patients before and after neoadjuvant chemotherapy, and the results before chemotherapy were validated in an independent cohort of 194 patients. The analyses revealed that in general the tumor characteristics are not reflected in the serum samples. However, there was an association of specific triacylglycerols (TGs) in patients' response to chemotherapy. These TGs containing mainly oleic acid (C18:1) were found in lower levels in those patients showing pathologic complete response before receiving chemotherapy. Some of these TGs were also associated with estrogen receptor status and overall or disease-free survival of the patients. The results suggest that the altered serum levels of oleic acid in breast cancer patients are associated with their response to chemotherapy.
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| 3. |
- Hilvo, Mika, et al.
(författare)
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Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression
- 2011
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Ingår i: Cancer Research. - Philadelphia, PA, USA : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 71:9, s. 3236-45
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Tidskriftsartikel (refereegranskat)abstract
- Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor-negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase α), ELOVL1 (elongation of very long chain fatty acid-like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element-binding protein cleavage-activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone-responsive protein)] indicated that silencing of multiple lipid metabolism-regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment.
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| 4. |
- Joukamo, Laura, et al.
(författare)
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Rasvainen kala muokkaa HDL-hiukkaskokoa ja lipidipitoisuuksia [Fatty fish modifies HDL particle size and lipid concentrations]
- 2013
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Ingår i: Duodecim. - : Duodecim. - 0012-7183 .- 2242-3281. ; 129:24, s. 2661-2670
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We investigated with 1HNMR-spectroscopy the effects of habitual fatty fish intake on serum lipiprotein profiles in persons with features of metabolic syndrome.MATERIAL AND METHODS: The participants (n = 105) were randomized into three diet intervention groups. The groups were given different dietary instructions.RESULTS: Increased intake of fatty fish had a significant (p < 0.05) increasing effect on the amount of large HDL-lipoprotein subclasses and their lipids.CONCLUSIONS: Frequent intake of fatty fish may have beneficial effects on HDL-metabolism beyond that assumed to be related to its serum concentrations.
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| 5. |
- Kajander, Kajsa, et al.
(författare)
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Elevated pro-inflammatory and lipotoxic mucosal lipids characterise irritable bowel syndrome
- 2009
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Co., Limited. - 1007-9327 .- 2219-2840. ; 15:48, s. 6068-6074
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate the pathophysiology of irritable bowel syndrome (IBS) by comparing the global mucosal metabolic profiles of IBS patients with those of healthy controls.METHODS: Fifteen IBS patients fulfilling the Rome II criteria, and nine healthy volunteers were included in the study. A combined lipidomics (UPLC/MS) and metabolomics (GC x GC-TOF) approach was used to achieve global metabolic profiles of mucosal biopsies from the ascending colon.RESULTS: Overall, lipid levels were elevated in patients with IBS. The most significant upregulation was seen for pro-inflammatory lysophosphatidylcholines. Other lipid groups that were significantly upregulated in IBS patients were lipotoxic ceramides, glycosphingolipids, and di- and triacylglycerols. Among the metabolites, the cyclic ester 2(3H)-furanone was almost 14-fold upregulated in IBS patients compared to healthy subjects (P = 0.03).CONCLUSION: IBS mucosa is characterised by a distinct pro-inflammatory and lipotoxic metabolic profile. Especially, there was an increase in several lipid species such as lysophospholipids and ceramides.
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| 6. |
- Karpanen, Terhi, et al.
(författare)
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Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy
- 2008
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Ingår i: Circulation Research. - : American Heart Association. - 0009-7330 .- 1524-4571. ; 103:9, s. 1018-1026
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF)-B is poorly angiogenic but prominently expressed in metabolically highly active tissues, including the heart. We produced mice expressing a cardiac-specific VEGF-B transgene via the alpha-myosin heavy chain promoter. Surprisingly, the hearts of the VEGF-B transgenic mice showed concentric cardiac hypertrophy without significant changes in heart function. The cardiac hypertrophy was attributable to an increased size of the cardiomyocytes. Blood capillary size was increased, whereas the number of blood vessels per cell nucleus remained unchanged. Despite the cardiac hypertrophy, the transgenic mice had lower heart rate and blood pressure than their littermates, and they responded similarly to angiotensin II-induced hypertension, confirming that the hypertrophy does not compromise heart function. Interestingly, the isolated transgenic hearts had less cardiomyocyte damage after ischemia. Significantly increased ceramide and decreased triglyceride levels were found in the transgenic hearts. This was associated with structural changes and eventual lysis of mitochondria, resulting in accumulation of intracellular vacuoles in cardiomyocytes and increased death of the transgenic mice, apparently because of mitochondrial lipotoxicity in the heart. These results suggest that VEGF-B regulates lipid metabolism, an unexpected function for an angiogenic growth factor.
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| 7. |
- Koistinen, Ville Mikael, et al.
(författare)
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Interlaboratory coverage test on plant food bioactive compounds and their metabolites by mass spectrometry-based untargeted metabolomics
- 2018
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Bioactive compounds present in plant-based foods, and their metabolites derived from gut microbiota and endogenous metabolism, represent thousands of chemical structures of potential interest for human nutrition and health. State-of-the-art analytical methodologies, including untargeted metabolomics based on high-resolution mass spectrometry, are required for the profiling of these compounds in complex matrices, including plant food materials and biofluids. The aim of this project was to compare the analytical coverage of untargeted metabolomics methods independently developed and employed in various European platforms. In total, 56 chemical standards representing the most common classes of bioactive compounds spread over a wide chemical space were selected and analyzed by the participating platforms (n = 13) using their preferred untargeted method. The results were used to define analytical criteria for a successful analysis of plant food bioactives. Furthermore, they will serve as a basis for an optimized consensus method.
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| 8. |
- Kotronen, Anna, et al.
(författare)
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Comparison of lipid and fatty acid composition of the liver, subcutaneous and intra-abdominal adipose tissue, and serum
- 2010
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Ingår i: Obesity. - : Wiley-Blackwell Publishing Inc.. - 1930-7381 .- 1930-739X. ; 18:5, s. 937-944
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Tidskriftsartikel (refereegranskat)abstract
- Ceramides may mediate saturated fat-induced insulin resistance, but there are no data comparing ceramide concentrations between human tissues. We therefore performed lipidomic analysis of human subcutaneous (SCfat) and intra-abdominal (IAfat) adipose tissue, the liver, and serum in eight subjects. The liver contained (nmol/mg tissue) significantly more ceramides (1.5-3-fold), sphingomyelins (7-8-fold), phosphatidylethanolamines (10-11-fold), lysophosphatidylcholines (7-12-fold), less ether-linked phosphatidylcholines (2-2.5-fold) but similar amounts of diacylglycerols as compared to SCfat and IAfat. The amounts of ceramides and their synthetic precursors, such as palmitic (16:0) free fatty acids and sphingomyelins, differed considerably between the tissues. The liver contained proportionally more palmitic, stearic (18:0), and long polyunsaturated fatty acids than adipose tissues. Stearoyl-CoA desaturase 1 (SCD1) activity reflected by serum, estimated from the 16:1/16:0-ratio, was closely related to that in the liver (r = 0.86, P = 0.024) but not adipose tissues. This was also true for estimated elongase (18:1/16:1, r = 0.89, P = 0.01), and Delta5 (20:4/20:3, r = 0.89, P = 0.012) and Delta6 (18:3[n-6]/18:2, r = 1.0, P < 0.001) desaturase activities. We conclude that the human liver contains higher concentrations of ceramides and saturated free fatty acids than either SCfat or IAfat.
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| 9. |
- Kotronen, Anna, et al.
(författare)
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Hepatic stearoyl-CoA desaturase (SCD)-1 activity and diacylglycerol but not ceramide concentrations are increased in the nonalcoholic human fatty liver
- 2009
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 58:1, s. 203-208
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether 1) hepatic ceramide and diacylglycerol concentrations, 2) SCD1 activity, and 3) hepatic lipogenic index are increased in the human nonalcoholic fatty liver.RESEARCH DESIGN AND METHODS: We studied 16 subjects with (n = 8) and without (n = 8) histologically determined nonalcoholic fatty liver (NAFL(+) and NAFL(-)) matched for age, sex, and BMI. Hepatic concentrations of lipids and fatty acids were quantitated using ultra-performance liquid chromatography coupled to mass spectrometry and gas chromatography.RESULTS: The absolute (nmol/mg) hepatic concentrations of diacylglycerols but not ceramides were increased in the NAFL(+) group compared with the NAFL(-) group. The livers of the NAFL(+) group contained proportionally less long-chain polyunsaturated fatty acids as compared with the NAFL(-) group. Liver fat percent was positively related to hepatic stearoyl-CoA desaturase 1 (SCD1) activity index (r = 0.70, P = 0.003) and the hepatic lipogenic index (r = 0.54, P = 0.030). Hepatic SCD1 activity index was positively related to the concentrations of diacylglycerols (r = 0.71, P = 0.002) but not ceramides (r = 0.07, NS).CONCLUSIONS: We conclude that diacylglycerols but not ceramides are increased in NAFL. The human fatty liver is also characterized by depletion of long polyunsaturated fatty acids in the liver and increases in hepatic SCD1 and lipogenic activities.
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| 10. |
- La Torre, Daria, et al.
(författare)
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Decreased cord-blood phospholipids in young age-at-onset type 1 diabetes
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 62:11, s. 3951-3956
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Tidskriftsartikel (refereegranskat)abstract
- Children developing type 1 diabetes may have risk markers already in their umbilical cord blood. It is hypothesized that the risk for type 1 diabetes at an early age may be increased by a pathogenic pregnancy and be reflected in altered cord-blood composition. This study used metabolomics to test if the cord-blood lipidome was affected in children diagnosed with type 1 diabetes before 8 years of age. The present case-control study of 76 index children diagnosed with type 1 diabetes before 8 years of age and 76 healthy control subjects matched for HLA risk, sex, and date of birth, as well as the mother's age and gestational age, revealed that cord-blood phosphatidylcholines and phosphatidylethanolamines were significantly decreased in children diagnosed with type 1 diabetes before 4 years of age. Reduced levels of triglycerides correlated to gestational age in index and control children and to age at diagnosis only in the index children. Finally, gestational infection during the first trimester was associated with lower cord-blood total lysophosphatidylcholines in index and control children. In conclusion, metabolomics of umbilical cord blood may identify children at increased risk for type 1 diabetes. Low phospholipid levels at birth may represent key mediators of the immune system and contribute to early induction of islet autoimmunity.
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| 11. |
- Laaksonen, Reijo, et al.
(författare)
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A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle
- 2006
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aggressive lipid lowering with high doses of statins increases the risk of statin-induced myopathy. However, the cellular mechanisms leading to muscle damage are not known and sensitive biomarkers are needed to identify patients at risk of developing statin-induced serious side effects.METHODOLOGY: We performed bioinformatics analysis of whole genome expression profiling of muscle specimens and UPLC/MS based lipidomics analyses of plasma samples obtained in an earlier randomized trial from patients either on high dose simvastatin (80 mg), atorvastatin (40 mg), or placebo.PRINCIPAL FINDINGS: High dose simvastatin treatment resulted in 111 differentially expressed genes (1.5-fold change and p-value<0.05), while expression of only one and five genes was altered in the placebo and atorvastatin groups, respectively. The Gene Set Enrichment Analysis identified several affected pathways (23 gene lists with False Discovery Rate q-value<0.1) in muscle following high dose simvastatin, including eicosanoid synthesis and Phospholipase C pathways. Using lipidomic analysis we identified previously uncharacterized drug-specific changes in the plasma lipid profile despite similar statin-induced changes in plasma LDL-cholesterol. We also found that the plasma lipidomic changes following simvastatin treatment correlate with the muscle expression of the arachidonate 5-lipoxygenase-activating protein.CONCLUSIONS: High dose simvastatin affects multiple metabolic and signaling pathways in skeletal muscle, including the pro-inflammatory pathways. Thus, our results demonstrate that clinically used high statin dosages may lead to unexpected metabolic effects in non-hepatic tissues. The lipidomic profiles may serve as highly sensitive biomarkers of statin-induced metabolic alterations in muscle and may thus allow us to identify patients who should be treated with a lower dose to prevent a possible toxicity.
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| 12. |
- Lankinen, Maria A., et al.
(författare)
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Dietary carbohydrate modification alters serum metabolic profiles in individuals with the metabolic syndrome
- 2010
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier. - 0939-4753 .- 1590-3729. ; 20:4, s. 249-57
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, but the mechanisms are poorly understood. We studied the effect of carbohydrate modification on serum metabolic profiles, including lipids and branched chain amino acids, and dependencies between these and specific gene expression pathways in adipose tissue.METHODS AND RESULTS: Twenty subjects with metabolic syndrome were selected from the larger FUNGENUT study population, randomized either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP). Serum metabolomics analyses were performed using ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry (UPLC/MS), gas chromatography (GC) and UPLC. In the OWP group multiple proinflammatory lysophosphatidylcholines increased, while in the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased. mRNA expression of stress reactions- and adipose tissue differentiation-related genes were up-regulated in adipose tissue in the OWP group. In the RP group, however, pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The lipid profiles had the strongest association with the changes in the adipose tissue differentiation pathway when using the elastic net regression model of the lipidomic profiles on selected pathways.CONCLUSION: Our results suggest that the dietary carbohydrate modification alters the serum metabolic profile, especially in lysoPC species, and may, thus, contribute to proinflammatory processes which in turn promote adverse changes in insulin and glucose metabolism.
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| 13. |
- Lankinen, Maria, et al.
(författare)
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A Healthy Nordic Diet Alters the Plasma Lipidomic Profile in Adults with Features of Metabolic Syndrome in a Multicenter Randomized Dietary Intervention
- 2016
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Ingår i: Journal of Nutrition. - New York, USA : Oxford University Press. - 0022-3166 .- 1541-6100. ; 146:4, s. 662-672
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A healthy Nordic diet is associated with improvements in cardiometabolic risk factors, but the effect on lipidomic profile is not known.OBJECTIVE: The aim was to investigate how a healthy Nordic diet affects the fasting plasma lipidomic profile in subjects with metabolic syndrome.METHODS: Men and women (n = 200) with features of metabolic syndrome [mean age: 55 y; body mass index (in kg/m(2)): 31.6] were randomly assigned to either a healthy Nordic (n = 104) or a control (n = 96) diet for 18 or 24 wk at 6 centers. Of the participants, 156 completed the study with plasma lipidomic measurements. The healthy Nordic diet consisted of whole grains, fruits, vegetables, berries, vegetable oils and margarines, fish, low-fat milk products, and low-fat meat. An average Nordic diet served as the control diet and included low-fiber cereal products, dairy fat-based spreads, regular-fat milk products, and a limited amount of fruits, vegetables, and berries. Lipidomic profiles were measured at baseline, week 12, and the end of the intervention (18 or 24 wk) by using ultraperformance liquid chromatography mass spectrometry. The effects of the diets on the lipid variables were analyzed with linear mixed-effects models. Data from centers with 18- or 24-wk duration were also analyzed separately.RESULTS: Changes in 21 plasma lipids differed significantly between the groups at week 12 (false discovery rate P < 0.05), including increases in plasmalogens and decreases in ceramides in the healthy Nordic diet group compared with the control group. At the end of the study, changes in lipidomic profiles did not differ between the groups. However, when the intervention lasted 24 wk, changes in 8 plasma lipids that had been identified at 12 wk, including plasmalogens, were sustained. There were no differences in changes in plasma lipids between groups with an intervention of 18 wk. By the dietary biomarker score, adherence to diet did not explain the difference in the results related to the duration of the study.CONCLUSIONS: A healthy Nordic diet transiently modified the plasma lipidomic profile, specifically by increasing the concentrations of antioxidative plasmalogens and decreasing insulin resistance-inducing ceramides. This trial was registered at clinicaltrials.gov as NCT00992641.
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| 14. |
- Lankinen, Maria, et al.
(författare)
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Fatty fish intake decreases lipids related to inflammation and insulin signaling : a lipidomics approach
- 2009
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The evidence of the multiple beneficial health effects of fish consumption is strong, but physiological mechanisms behind these effects are not completely known. Little information is available on the effects of consumption of different type of fish. The aim of this study was to investigate how fatty fish or lean fish in a diet affect serum lipidomic profiles in subjects with coronary heart disease.METHODOLOGY AND PRINCIPAL FINDINGS: A pilot study was designed which included altogether 33 subjects with myocardial infarction or unstable ischemic attack in an 8-week parallel controlled intervention. The subjects were randomized to either fatty fish (n = 11), lean fish (n = 12) or control (n = 10) groups. Subjects in the fish groups had 4 fish meals per week and subjects in the control group consumed lean beef, pork and chicken. A fish meal was allowed once a week maximum. Lipidomics analyses were performed using ultra performance liquid chromatography coupled to electrospray ionization mass spectrometry and gas chromatography. Multiple bioactive lipid species, including ceramides, lysophosphatidylcholines and diacylglycerols, decreased significantly in the fatty fish group, whereas in the lean fish group cholesterol esters and specific long-chain triacylglycerols increased significantly (False Discovery Rate q-value <0.05).CONCLUSIONS/SIGNIFICANCE: The 8-week consumption of fatty fish decreased lipids which are potential mediators of lipid-induced insulin resistance and inflammation, and may be related to the protective effects of fatty fish on the progression of atherosclerotic vascular diseases or insulin resistance.TRIAL REGISTRATION: ClinicalTrials.gov NCT00720655.
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| 15. |
- Lankinen, Maria, et al.
(författare)
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Metabolomic analysis of plasma metabolites that may mediate effects of rye bread on satiety and weight maintenance in postmenopausal women
- 2011
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Ingår i: Journal of Nutrition. - : Oxford University Press. - 0022-3166 .- 1541-6100. ; 141:1, s. 31-36
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Tidskriftsartikel (refereegranskat)abstract
- The evidence of the beneficial health effects of dietary fiber and whole grain consumption is strong, but the underlying mechanisms are not completely understood. Here, we investigate how the consumption of high-fiber rye bread (RB) or white-wheat bread (WB) modifies the plasma metabolomic profiles in postmenopausal women. The study was a randomized crossover trial consisting of 8-wk intervention periods and an 8-wk washout period. The study included 39 postmenopausal women with elevated serum total cholesterol (5.0-8.5 mmol/L) and BMI 20-33 kg/m(2). During the intervention periods, the study breads contributed to least 20% of total energy intake. Two analytical platforms for metabolomics were applied. Lipidomic analysis was performed using ultra performance liquid chromatography coupled to electrospray ionization MS and the other metabolites, including sterols, organic acids, and alcohols, were analyzed by 2-dimensional GC coupled to time-of-flight MS. Altogether, 540 metabolites were profiled. Ribitol (P < 0.001), ribonic acid (P < 0.001), and indoleacetic acid (P < 0.001) increased during the RB consumption period. Ribonic acid correlated positively with tryptophan (r = 0.40; P = 0.003), which is a precursor for the biosynthesis of hunger-depressing serotonin. There were no changes in plasma lipidomic profiles during the RB or WB intervention periods. The results suggest that 8-wk consumption of high-fiber rye bread increases metabolites that might mediate positive effects of rye bread on satiety and weight maintenance.
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| 16. |
- Lankinen, Maria, et al.
(författare)
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Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial : the Sysdimet study
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism.METHODOLOGY/PRINCIPAL FINDINGS: Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1) whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group), (2) Whole grain enriched diet (WGED) group, which includes principally the same grain products as group (1), but with no change in fish or berry consumption, and (3) refined wheat breads (Control). Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3) long-chain PUFAs increased (False Discovery Rate p-values <0.05). Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3) PUFA.CONCLUSIONS/SIGNIFICANCE: The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a beneficial effect in the efforts to prevent type 2 diabetes in high risk persons.TRIAL REGISTRATION: ClinicalTrials.gov NCT00573781.
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| 17. |
- Leskinen, Tuija, et al.
(författare)
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Differences in muscle and adipose tissue gene expression and cardio-metabolic risk factors in the members of physical activity discordant twin pairs
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50-74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased 'high-risk' ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are associated with reduced cardio-metabolic risk.
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| 18. |
- Mattila, Ismo, et al.
(författare)
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Application of lipidomics and metabolomics to the study of adipose tissue
- 2008
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Ingår i: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1064-3745 .- 1940-6029. ; 456, s. 123-130
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Tidskriftsartikel (refereegranskat)abstract
- Role of specific reactive lipids as well as amino acids in control of insulin signalling in adipose tissue is well recognized. Since it is practically impossible to measure the levels of all metabolites in the biological sample simultaneously with a single analytical platform, we utilize multiple platforms to study the lipids and metabolites of relevance to adipose tissue metabolism and insulin signalling. Two screening platforms cover a broad range of lipid molecular species (UPLC/MS based lipidomics platform) as well as organic acids and sterols (GCxGC-TOF platform). A targeted platform for amino acids (UPLC) is also applied.
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| 19. |
- Medina-Gomez, Gema, et al.
(författare)
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PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism
- 2007
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2(-/-) Lep(ob)/Lep(ob) (POKO mouse), resulted in decreased fat mass, severe insulin resistance, beta-cell failure, and dyslipidaemia. Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species. Our data also indicate that PPARg2 may be required for the beta-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a) promoting adipose tissue expansion, (b) increasing the lipid-buffering capacity of peripheral organs, and (c) facilitating the adaptive proliferative response of beta-cells to insulin resistance.
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| 20. |
- Medina-Gomez, Gema, et al.
(författare)
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The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-gamma2 isoform
- 2005
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:6, s. 1706-1716
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) is critically required for adipogenesis. PPARgamma exists as two isoforms, gamma1 and gamma2. PPARgamma2 is the more potent adipogenic isoform in vitro and is normally restricted to adipose tissues, where it is regulated more by nutritional state than PPARgamma1. To elucidate the relevance of the PPARgamma2 in vivo, we generated a mouse model in which the PPARgamma2 isoform was specifically disrupted. Despite similar weight, body composition, food intake, energy expenditure, and adipose tissue morphology, male mice lacking the gamma2 isoform were more insulin resistant than wild-type animals when fed a regular diet. These results indicate that insulin resistance associated with ablation of PPARgamma2 is not the result of lipodystrophy and suggests a specific role for PPARgamma2 in maintaining insulin sensitivity independently of its effects on adipogenesis. Furthermore, PPARgamma2 knockout mice fed a high-fat diet did not become more insulin resistant than those on a normal diet, despite a marked increase in their mean adipocyte cell size. These findings suggest that PPARgamma2 is required for the maintenance of normal insulin sensitivity in mice but also raises the intriguing notion that PPARgamma2 may be necessary for the adverse effects of a high-fat diet on carbohydrate metabolism.
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| 21. |
- Nikkilä, Janne, et al.
(författare)
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Gender-dependent progression of systemic metabolic states in early childhood
- 2008
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Ingår i: Molecular Systems Biology. - : Nature Publishing Group. - 1744-4292 .- 1744-4292. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the human intra-individual metabolic profile changes over an extended period of time. Here, we introduce a novel concept suggesting that children even at a very young age can be categorized in terms of metabolic state as they advance in development. The hidden Markov models were used as a method for discovering the underlying progression in the metabolic state. We applied the methodology to study metabolic trajectories in children between birth and 4 years of age, based on a series of samples selected from a large birth cohort study. We found multiple previously unknown age- and gender-related metabolome changes of potential medical significance. Specifically, we found that the major developmental state differences between girls and boys are attributed to sphingolipids. In addition, we demonstrated the feasibility of state-based alignment of personal metabolic trajectories. We show that children have different development rates at the level of metabolome and thus the state-based approach may be advantageous when applying metabolome profiling in search of markers for subtle (patho)physiological changes.
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| 22. |
- Nygren, Heli, et al.
(författare)
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Liquid chromatography-mass spectrometry (LC-MS)-based lipidomics for studies of body fluids and tissues
- 2011
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Ingår i: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1064-3745 .- 1940-6029. ; 708, s. 247-257
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, analytical methodologies for the global profiling of lipids in serum and tissue samples are reported. The sample preparation is based on a modified Folch extraction, and the analysis is carried out with ultrahigh-performance liquid chromatography combined with mass spectrometry (UPLC-MS). For further identification, MS(n) mass spectrometry is carried out utilizing an LTQ-Orbitrap mass spectrometry as the detector. Such a system affords determination of accurate masses and is thus a highly useful tool for lipid identification. The repeatability of the analysis proved to be good, with relative standard errors for spiked samples being between 4.51 and 10.44%. The throughput of the methodology described here is over 100 samples a day.
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| 23. |
- Nygren, Heli, et al.
(författare)
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Ultrahigh-performance liquid chromatography-mass spectrometry in lipidomics
- 2013
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Ingår i: LC GC Europe. - : Advanstar Communications. - 1471-6577. ; 26:3, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- The analytical method for the global profiling of molecular lipids in biological samples, with particular emphasis on the plasmalogen lipids is described. The global profiling method is based on ultrahigh-performance liquid chromatography combined with quadrupole time-of-flight-mass spectrometry (UHPLC-QTOF-MS). The profiling approach is complemented by UHPLC-LTQ-Orbitrap mass spectrometry in MSn mode for de novo lipid identification.
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| 24. |
- Nygren, Heli, et al.
(författare)
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Ultrahigh-performance liquid chromatography-mass spectrometry in Lipidomics
- 2014
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Ingår i: LC GC North America. - : Advanstar Communications. - 1527-5949 .- 1939-1889. ; 32:4, s. 286-293
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Tidskriftsartikel (refereegranskat)abstract
- An analytical method for the global profiling of molecular lipids in biological samples, with particular emphasis on the plasmalogen lipids, is described. The global profiling method is based on ultrahigh-performance liquid chromatography combined with quadrupole time-of-flight-mass spectrometry (UHPLC-QTOE-MS). The profiling approach is complemented by UHPLC-LTQ-Orbitrap mass spectrometry in MSn mode for de novo lipid identification.
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| 25. |
- Oresic, Matej, 1967-, et al.
(författare)
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Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes
- 2008
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Ingår i: Journal of Experimental Medicine. - New York, USA : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 205:13, s. 2975-2984
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Tidskriftsartikel (refereegranskat)abstract
- The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward beta cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative. Individuals who developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow up, and increased levels of proinflammatory lysoPCs several months before seroconversion to autoantibody positivity. The lipid changes were not attributable to HLA-associated genetic risk. The appearance of insulin and glutamic acid decarboxylase autoantibodies was preceded by diminished ketoleucine and elevated glutamic acid. The metabolic profile was partially normalized after the seroconversion. Autoimmunity may thus be a relatively late response to the early metabolic disturbances. Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies.
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