O'Donovan2022 - the Mixed Meal Model
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ABSTRACT:
SUBMITTER: 
Shauna O'Donovan
PROVIDER: MODEL2212300001 | BioModels | 2022-12-31
REPOSITORIES: BioModels
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Project description:High fat diet (HF) rodent models have contributed significantly to the dissection of the pathophysiology of the insulin resistance syndrome, but their phenotype varies distinctly between different studies. Here, we have analyzed gene expression patterns in livers of animals fed with different HF with varying fatty acid compositions. Experiment Overall Design: Male Wistar rats were fed with high fat diets (42 energy%, fat sources: lard, olive oil; coconut fat; cod liver oil). Weight, food intake, whole body insulin tolerance and plasma parameters of glucose and lipid metabolism were measured during a 12 week diet course. Liver histologies and hepatic gene expression profiles using AffymetrixR gene chips were obtained.
2007-10-10 | E-GEOD-3512 | biostudies-arrayexpress
Project description:There is increased interest in the potential protective role of dietary Ca in the development of metabolic disorders related to the metabolic syndrome. Ca-induced intestinal precipitation of fatty acids and bile acids as well as systemic metabolic effects of Ca on adipose tissue is proposed to play a causal role. In this experiment, we have studied all these aspects to validate the suggested protective effect of Ca supplementation, independent of other dietary changes, on the development of diet-induced obesity and insulin resistance. In our diet intervention study, C57BL/6J mice were fed high-fat diets differing in Ca concentrations (50 v. 150 mmol/kg). Faecal excretion analyses showed an elevated precipitation of intestinal fatty acids (2·3-fold; P < 0·01) and bile acids (2-fold; P < 0·01) on the high-Ca diet. However, this only led to a slight reduction in fat absorption (from 98 to 95 %; P < 0·01), mainly in the distal small intestine as indicated by gene expression changes. We found no effect on body-weight gain. Lipolysis and lipogenesis-related parameters in adipose tissue also showed no significant changes on the high-Ca diet, indicating no systemic effects of dietary Ca on adiposity. Furthermore, early gene expression changes of intestinal signaling molecules predicted no protective effect of dietary Ca on the development of insulin resistance, which was confirmed by equal values for insulin sensitivity on both diets. Taken together, our data do not support the proposed protective effect of dietary Ca on the development of obesity and/or insulin resistance, despite a significant increase in fecal excretion of fatty acids and bile acids. Keywords: Diet intervention study Nine-week-old mice were fed a high fat purified diet with a low calcium concentration of 50mmol/kg (LCa diet) or a high calcium concentration of 150mmol/kg (HCa diet) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. For microarray analysis, after 2 weeks of diet intervention, 6 mice per diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on pooled mucosal scrapings.
2011-03-03 | E-GEOD-18581 | biostudies-arrayexpress
Project description:Analysis of glucose and Lipid metabolism in male and female offspring after protein restriction of the mother Male offspring showed features of metabolic syndrome after receiving a high fat diet, regardless of the diet of the dam. Glucose and lipid metabolism in male offspring was unaltered. Insulin sensitivity and hepatic fatty acid storage in female offspring of low-protein-fed dams changed in such a way that it resembled the male pattern of insulin sensitivity and hepatic fatty acid storage. Microarray analysis on hepatic gene expression patterns confirmed these findings. We therefore conclude that in mice, maternal protein restriction does not change the response of glucose and fatty acid metabolism to a high fat diet in male offspring, but does program metabolism in female offspring in such a way that it resembles male metabolism. Our findings might have implications for potential future gender-specific treatment of the features of metabolic diseases. Total RNA obtained from liver (16 samples per gender) were compared in the different groups. In total, 4 groups per gender, each group consisting of 4 biological replicates.
2012-02-08 | E-GEOD-15940 | biostudies-arrayexpress
Project description:Metabolic dysfunctions, such as fatty liver, obesity and insulin resistance, are among the most common contemporary diseases worldwide. Mimp/Mtch2 is a mitochondrial carrier protein homologue that leads to mitochondrial depolarization, localizes to the mitochondria and induces accumulation of fat vesicles. Transgenic mice overexpressing Mimp/Mtch2 develop fatty livers and kidneys and exhibit high blood glucose levels. The mechanism of lipid accumulation in the kidney has not been fully determined. In this study we performed a differential gene expression profile of fatty compared to non-fatty kidneys of Mimp/Mtch2-GFP transgenic mice, fed on high fat diet. RNA samples for microarray gene expression profiling were obtained from four Mimp/Mtch2-GFP mice, two samples of low fat kidneys and two of fatty kidneys.
2016-06-15 | E-MTAB-1752 | biostudies-arrayexpress
Project description:Inactivating mutations in the copper transporter Atp7b result in Wilson’s disease. The Atp7b-/- mouse develops hallmarks of Wilson’s disease. The activity of several nuclear receptors is decreased in Atp7b-/- mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b-/- mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 weeks on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by LC-MS and correlated with transcriptomic data. Atp7b-/- mice fed a chow diet had lower fat mass and were more glucose tolerant than wild type (WT) littermate controls although body weights did not differ between genotypes. On Western diet, Atp7b-/- mice exhibited reduced adiposity and hepatic steatosis compared with WT controls. Atp7b-/- mice fed either diet were more insulin sensitive than WT controls; however, fasted Atp7b-/- mice exhibited hypoglycemia after administration of insulin, due to an impaired glucose counter-regulatory response, as evidenced by reduced hepatic glucose production. Coupling gene expression with metabolomic analyses, we observed striking changes in hepatic metabolic profiles in Atp7b-/- mice. In addition, the active phosphorylated form of AMP kinase was significantly increased in Atp7b-/- mice relative with WT controls. Alterations in hepatic metabolic profiles and nuclear receptor signaling were associated with improved glucose tolerance and insulin sensitivity, as well as impaired fasting glucose production in Atp7b-/- mice.
2020-04-14 | GSE125637 | GEO
Project description:Analysis of glucose and Lipid metabolism in male and female offspring after protein restriction of the mother Male offspring showed features of metabolic syndrome after receiving a high fat diet, regardless of the diet of the dam. Glucose and lipid metabolism in male offspring was unaltered. Insulin sensitivity and hepatic fatty acid storage in female offspring of low-protein-fed dams changed in such a way that it resembled the male pattern of insulin sensitivity and hepatic fatty acid storage. Microarray analysis on hepatic gene expression patterns confirmed these findings. We therefore conclude that in mice, maternal protein restriction does not change the response of glucose and fatty acid metabolism to a high fat diet in male offspring, but does program metabolism in female offspring in such a way that it resembles male metabolism. Our findings might have implications for potential future gender-specific treatment of the features of metabolic diseases.
2012-02-08 | GSE15940 | GEO
Project description:Defective insulin secretion by pancreatic β cells underlies the development of type 2 diabetes (T2D). High fat diet-fed mice are commonly used to study diabetes progression, but studies are usually limited to a single strain, such as C57Bl/6J. Here, we use a systems biology approach to integrate large phenotypic and islet transcriptomic data sets from six commonly used strains fed a high fat or regular chow diet to identify genes associated with glucose intolerance and insulin secretion. One of these genes is Elovl2, encoding very long chain fatty acid elongase 2. ELOVL2 is responsible for the synthesis of the polyunsaturated fatty acid, docosahexaenoic acid (DHA). We show that DHA rescues glucose-induced insulin secretion and cytosolic Ca2+ influx impaired by glucolipotoxicity, and that Elovl2 over-expression is able to restore the insulin secretion defect under these conditions. We propose that increased endogenous DHA levels resulting from Elovl2 up-regulation counteracts the insulin secretion defect associated with glucolipotoxicity. Although we focus our experimental validation on Elovl2, the comprehensive data set and integrative network model we used to identify this candidate gene represents an important novel resource to dissect the molecular aetiology of β cell failure in murine models. 6 mouse strains, 4 time points, 2 diets
2017-04-28 | E-GEOD-78183 | biostudies-arrayexpress
Project description:From a long time ago, supplementation of fermented enzyme foods could have worked health effects on the body in the east nevertheless, only a few studies reported functions of them such as weight loss and metabolic syndrome. Thus, it is necessary to be verified whether supplementation of fermented enzyme foods can act in the body as a functional material. Therefore, we investigated the anti-obesity effects of fermented mixed grain with digestive enzymes (FMG) in high-fat diet induced mice. Sixty C57BL/6J mice were divided into six dietary groups and fed a normal diet (ND), a high-fat diet (HFD), Bacilus Coagulans group, steamed grain group, low-dose fermented mixed grain group(L-FMG), high-dose fermented mixed grain group (H-FMG) supplement for 12 weeks. After sacrificing, body weight and body fat mass in H-FMG group were significantly decreased compared to HFD group with a simultaneous decrease in plasma lipids. Also, H-FMG significantly decreased the blood glucose and improved the glucose tolerance compared to HFD group. Moreover high-dose FMG supplementation dramatically decreased the levels of inflammatory cytokines which secreted from adipocyte. Taken together, our findings suggest that H-FMG ameliorate high fat-diet induced obesity and its complication and could be used as a potential preventive agent for obesity.
2020-09-12 | GSE157822 | GEO
Project description:Physical inactivity and western diet are the main factors leading to skeletal muscle (and whole-body) insulin resistance – a defect in insulin-mediated glucose uptake and metabolism – and associated metabolic diseases, such as obesity and type 2 diabetes mellitus (T2D). The study of the response to a mixed meal (normalized for body mass and/or basal metabolic rate) is of particular interest, as it simulates the physiological response to a typical (daily) single meal that depends on both the secretory function of the beta cells (insulin response) and the sensitivity of skeletal muscle signaling to insulin – variables, which markedly changing during development of insulin resistance and T2D. We aimed to compare the early transcriptomic response to a mixed meal normalized to body mass in skeletal muscle of healthy subjects and obese patients without (Ob) and with T2D (Ob+T2D). To investigate the early transcriptomic response we took biopsy samples from the vastus lateralis muscle prior to and 1 h after a meal. In the Ob+T2D group the average level and increase in C-peptide and insulin in the blood were comparable with healthy subjects that, apparently, is explained by dysfunction of the beta-cells induced by chronic T2D. At the same time, the Ob+T2D group demonstrated dysregulation of mixed meal-induced gene expression in skeletal muscle: morу than two times lower number of DEGs and a small overlapping with the gene response in the control group. On the contrary, the postprandial level of C-peptide and insulin in the Ob group was significantly greater than in healthy control that is related to insulin oversecretion associated with insulin resistance. Despite this, the gene response in skeletal muscle was also significantly dysregulated; moreover, it differed from the response in the Ob+T2D group. It means that defect in regulation of insulin-induced gene expression (insulin resistance in terms of gene expression) appears at the first stage of the development of metabolic disorders.
2023-05-05 | GSE231509 | GEO
Project description:Dysregulated glucose homeostasis and lipid accumulation characterize non-alcoholic fatty liver disease (NAFLD), but underlying mechanisms are obscure. We report here that Krüppel-like factor 6 (KLF6), a ubiquitous transcription factor that promotes adipocyte differentiation, also provokes the metabolic abnormalities of NAFLD. Mice with either hepatocyte-specific knockdown of KLF6 (DeltaHepKlf6) or global KLF6 heterozygosity (Klf6 +/-) have reduced body fat content and improved glucose and insulin tolerance. Mice with KLF6 depletion, compared to wild type mice, are protected from high fat diet-induced steatosis.
2012-03-23 | GSE36724 | GEO