Holdemanella biformis oral adminstration improves glucose tolerance
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ABSTRACT:
PROVIDER: PRJEB38356 | ENA |
REPOSITORIES: ENA
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2019-06-03 | GSE93546 | GEO
Project description:The gut microbiome is a key factor regulating energy-metabolism, glucose tolerance and the immune system. Akkermansia muciniphila has been identified as being beneficial gut bacterium for metabolic diseases, including obesity and type 2 diabetes (T2D); however, the molecular mechanisms involved in host interactions have yet to be known. Here, we described the effects of A. muciniphila on thermogenesis and GLP-1 secretion through the specific secretory protein produced by A. muciniphila and its mode of action. A. muciniphila significantly elevated thermogenesis with induction of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) and systemic glucagon-like peptide-1 (GLP-1) secretion. Using fast protein liquid chromatography (FPLC) and liquid chromatography (LC)-mass spectrophotometry (MS)/MS analysis, we discovered that a novel 84-kDa protein, P9 is secreted by A. muciniphila and this protein improves obesity and glucose tolerance by inducing GLP-1 secretion and BAT thermogenesis. P9 induces GLP-1 secretion with direct interaction with the specific host protein, intercellular adhesion molecule-2 (ICAM-2), via IL-6 dependent pathway. This novel host-microbe interaction between P9 and ICAM-2 may become a therapeutic target for metabolic diseases.
2021-01-13 | MTBLS1824 | MetaboLights
Project description:Natural killer T (NKT) cells are important therapeutic targets in various disease models and under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type-1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high-fat diet (HFD) feeding, activation of NKT cells by lipid agonist α-galactosylceramide (αGalCer) enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identifies a novel therapeutic target for the treatment of obesity-associated inflammation and type-2 diabetes. Wild type and CD1d1 antigen (CD1d) knockout mice were fed a high fat diet for 4 days. On day 0 and 2 mice were injected intraperitoneally with α-galactosylceramide (αGalCer) or vehicle. On day 4 mice were killed and gene expression was profiled in epididymal adipose tissue.
2012-04-12 | E-GEOD-36032 | biostudies-arrayexpress
Project description:Natural killer T (NKT) cells are important therapeutic targets in various disease models and under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type-1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high-fat diet (HFD) feeding, activation of NKT cells by lipid agonist α-galactosylceramide (αGalCer) enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identifies a novel therapeutic target for the treatment of obesity-associated inflammation and type-2 diabetes.
2012-04-13 | GSE36032 | GEO
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2013-01-02 | E-GEOD-41168 | biostudies-arrayexpress
Project description:The study group consisted of 17 obese women with normal glucose tolerance and 15 obese women with T2DM. Adipose tissue specimens were taken from the epigastric region of the abdominal wall (SAT) and from the major omentum (VAT). RNA was isolated and RNA sequencing was used to analyse the transcriptome. Dharuri H et al, Diabetologia. 2014;57(11):2384-92.
| EGAS00001001872 | EGA
Project description:A greater understanding of the glucose homeostasis mediated by glucagon-like peptide-1 (GLP-1) will facilitate the development of novel glucose-lowering treatments. Here we show that improved glucose metabolism in hypothyroid mice after treatment of T3, the active form of thyroid hormone (TH), is accompanied with increased GLP-1 production and insulin secretion. Treatment of a GLP-1 receptor antagonist is able to attenuate the observed T3 effect on insulin and glucose levels, suggesting that GLP-1 is critically involved in the regulation of glucose homeostasis by T3. By using a mouse model lacking hepatic TH receptor β (TRβ) and a liver-specific TRβ-selective agonist, we demonstrate that TRβ-mediated hepatic TH signalling is not only required for the regulation of GLP-1 production by T3 but also the insulinotropic and glucose-lowering effects of T3. Accordingly, administration of the liver-targeted TRβ-selective agonist is capable of increasing GLP-1 and insulin levels and alleviating hyperglycemia in diet-induced obesity. Mechanistically, through suppressing CYP8B1 expression, T3 shapes the bile acid (BA) composition and increases the levels of Farnesoid X receptor (FXR)-antagonistic BAs, thereby potentiating the GLP-1 production and insulin secretion by repressing intestinal FXR signalling. Consistently, correlations between the T3 levels and either GLP-1 or FXR-antagonistic BA levels can be observed in euthyroid human subjects. Thus, our study reveals a previously undescribed role of hepatic TH signalling in glucose homeostasis through the regulation of GLP-1 production via BA-mediated FXR antagonism, which will underpin the development of novel therapeutics.
2022-09-23 | GSE184055 | GEO
Project description:Resveratrol has been reported to improve metabolic function in metabolically-abnormal rodents and humans, but has not been studied in non-obese people with normal glucose tolerance. We conducted a randomized, double-blind, placebo-controlled trial to evaluate the metabolic effects of 12 weeks of resveratrol supplementation (75 mg/day) in non-obese, postmenopausal women with normal glucose tolerance. Although resveratrol supplementation was well-tolerated and increased plasma resveratrol concentration without adverse effects, it did not change body composition, resting metabolic rate, plasma lipids, or inflammatory markers. A two-stage hyperinsulinemic-euglycemic clamp procedure, in conjunction with stable isotopically-labeled tracer infusions, demonstrated that resveratrol did not increase liver, skeletal muscle, or adipose tissue insulin sensitivity. Consistent with the absence of in vivo metabolic effects, resveratrol did not affect its putative molecular targets, including AMPK, Sirt1, Nampt, and Pgc-1α, in either skeletal muscle or adipose tissue. These findings demonstrate that resveratrol supplementation does not have metabolic effects in non-obese women.
2013-01-02 | GSE41168 | GEO
Project description:A greater understanding of the glucose homeostasis mediated by glucagon-like peptide-1 (GLP-1) will facilitate the development of novel glucose-lowering treatments. Here we show that improved glucose metabolism in hypothyroid mice after treatment of T3, the active form of thyroid hormone (TH), is accompanied with increased GLP-1 production and insulin secretion. Treatment of a GLP-1 receptor antagonist is able to attenuate the observed T3 effect on insulin and glucose levels, suggesting that GLP-1 is critically involved in the regulation of glucose homeostasis by T3. By using a mouse model lacking hepatic TH receptor β (TRβ) and a liver-specific TRβ-selective agonist, we demonstrate that TRβ-mediated hepatic TH signalling is not only required for the regulation of GLP-1 production by T3 but also the insulinotropic and glucose-lowering effects of T3. Accordingly, administration of the liver-targeted TRβ-selective agonist is capable of increasing GLP-1 and insulin levels and alleviating hyperglycemia in diet-induced obesity. Mechanistically, through suppressing CYP8B1 expression, T3 shapes the bile acid (BA) composition and increases the levels of Farnesoid X receptor (FXR)-antagonistic BAs, thereby potentiating the GLP-1 production and insulin secretion by repressing intestinal FXR signalling. Consistently, correlations between the T3 levels and either GLP-1 or FXR-antagonistic BA levels can be observed in euthyroid human subjects. Thus, our study reveals a previously undescribed role of hepatic TH signalling in glucose homeostasis through the regulation of GLP-1 production via BA-mediated FXR antagonism, which will underpin the development of novel therapeutics.
2022-09-23 | GSE184261 | GEO
Project description:Meal frequency regulates postprandial glucose and insulin responses, which may affect substrate partitioning and thus weight control. This study investigated the effects of meal frequency on the metabolic and transcriptomic profiles in subjects with impaired glucose tolerance (IGT). Eleven IGT (2h glucose; 9.0±0.3mmol/L) men stayed 2x 36 hours in a respiration chamber to measure substrate partitioning. All subjects randomly received two isoenergetic diets with a low meal frequency (3x-LFr) or a high meal frequency (14x-HFr) consisting of 15 En% prot, 30 En% fat, and 55 En% carb. Total glucose output (AUC), carbohydrate oxidation and whole body RQ significantly decreased, and FFA levels increased in the LFr diet. The HFr diet resulted in an up-regulation in expression of genes involved in immune function and inflammation after 24h in PBMCs and muscle tissue. Expression of genes involved in PPAR signalling, OXPHOS, and glutathione metabolism were up-regulated in the HFr diet in muscle tissue only. In conclusion, the LFr diet improved the metabolic and transcriptomic profiles, and appetite control compared to the HFr diet. This suggests that a LFr diet might be an effective dietary strategy with anti-inflammatory characteristics to increase metabolic flexibility and body weight control in IGT subjects.
2020-11-01 | GSE52026 | GEO