| 1. |
- Andersson, Kristina E, et al.
(author)
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Diverse effects of oats on cholesterol metabolism in C57BL/6 mice correlate with expression of hepatic bile acid-producing enzymes.
- 2013
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In: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 52:7, s. 1755-1769
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Journal article (peer-reviewed)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.
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| 2. |
- Axling, Ulrika, et al.
(author)
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A low glycaemic diet improves oral glucose tolerance but has no effect on β-cell function in C57BL/6J mice.
- 2010
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 12:11, s. 976-982
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Journal article (peer-reviewed)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.
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| 3. |
- Axling, Ulrika, et al.
(author)
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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
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In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 66:5, s. 585-590
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Journal article (peer-reviewed)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.
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| 4. |
- Axling, Ulrika
(author)
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Exploring food concepts for the prevention of type 2 diabetes
- 2011
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Doctoral thesis (other academic/artistic)abstract
- There is currently a dramatic and global increase in obesity, type 2 diabetes (T2D) and associated metabolic disorders. T2D can be delayed or prevented in individuals at risk and identifying and developing new food concepts for the prevention of obesity and T2D is of utmost importance. This thesis describes our work on exploring new food concepts for the prevention of T2D. We have used 3T3-L1 adipocytes, and C57BL/6J mice as experimental models and we have also carried out an intervention study in humans. We found that whole grain rye is better at preventing body weight gain than whole grain wheat in C57BL/6J mice fed a low-fat diet. The lower body weight reflected reduced adiposity and smaller adipocyte size and was accompanied by lower levels of circulating leptin. The reduction in adiposity could not be explained by alterations in the expression of genes involved in adipogenesis or lipogenesis. Furthermore, whole grain rye lowered plasma cholesterol and triacylglycerol, unlike whole grain wheat. Whole grain rye contains several bioactive components, including alkylresorcinols (ARs). We showed that ARs isolated from rye bran suppress catecholamine-stimulated lipolysis in 3T3-L1 adipocytes. Obesity and insulin-resistant states are often characterised by a dysfunctional adipose tissue with insufficient trapping of fatty acids. Our results suggest that intake of ARs could lead to lower levels of circulating fatty acids in vivo which could have beneficial effects in relation to insulin resistance. Furthermore, we showed that a large dose of rose hip induces several beneficial metabolic effects in mice, including anti-obesity effects, reduced hepatic lipid accumulation, reduced plasma cholesterol and improved glucose tolerance. The reduced hepatic lipid accumulation was accompanied by lowered plasma alanine aminotransferase levels, and was associated with a down-regulation of the hepatic lipogenic programme. However, lower doses of rose hip failed to induce anti-obesity effects in obese non-diabetic humans. Also, no effect of rose hip on glucose tolerance was observed in humans, probably due to the lack of effect on adiposity. However, rose hip induced a reduction in total plasma cholesterol as well as in the LDL to HDL ratio in both mice and humans. The beneficial effects of rose hip could be attributed to increased faecal excretion of both triacylglycerol and cholesterol.
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| 5. |
- Axling, Ulrika, et al.
(author)
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Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice
- 2012
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In: Nutrition & Metabolism. - : Springer Science and Business Media LLC. - 1743-7075. ; 9:105
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Journal article (peer-reviewed)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.
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| 6. |
- Axling, Ulrika, et al.
(author)
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Increased whole body energy expenditure and protection against diet-induced obesity in Cyp8b1-deficient mice is accompanied by altered adipose tissue features
- 2020
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In: Adipocyte. - : TAYLOR & FRANCIS INC. - 2162-3945 .- 2162-397X. ; 9:1, s. 587-599
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Journal article (peer-reviewed)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.
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| 7. |
- Axling, Ulrika, et al.
(author)
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Metabolic effects of whole grain wheat and whole grain rye in the C57BL/6J mouse.
- 2010
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In: Nutrition. - : Elsevier BV. - 1873-1244 .- 0899-9007. ; 26, s. 230-239
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Journal article (peer-reviewed)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.
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| 8. |
- Axling, Ulrika, et al.
(author)
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Probiotics lower plasma glucose in the high-fat fed C57BL/6J mouse.
- 2010
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In: Beneficial microbes. - 1876-2891. ; 1:2, s. 189-196
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Journal article (peer-reviewed)abstract
- Today, the gut microbiota is considered a key organ in host nutritional metabolism and recent data have suggested that alterations in gut microbiota contribute to the development of type 2 diabetes and obesity. Accordingly, a whole range of beneficial effects relating to inflammation and gut health have been observed following administration of probiotics to both humans and different animal models. The objective of this study was to evaluate the metabolic effects of an oral probiotic supplement, Lactobacillus plantarum DSM 15313, to high-fat diet (HFD) fed C57BL/6J mice, a model of human obesity and early diabetes. The mice were fed the experimental diets for 20 weeks, after which the HFD had induced an insulin-resistant state in both groups compared to the start of the study. The increase in body weight during the HFD feeding was higher in the probiotic group than in the control group, however, there were no significant differences in body fat content. Fasting plasma glucose levels were lower in the group fed the probiotic supplement, whereas insulin and lipids were not different. Caecal levels of short-chain fatty acids were not significantly different between the groups. An oral glucose tolerance test showed that the group fed probiotics had a significantly lower insulin release compared to the control group, although the rate of glucose clearance was not different. Taken together, these data indicate that L. plantarum DSM 15313 has anti-diabetic properties when fed together with an HFD.
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| 9. |
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| 10. |
- Axling, Ulrika, et al.
(author)
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Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program
- 2011
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In: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 300:1, s. 111-121
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Journal article (peer-reviewed)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.
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