The alpha-glucosidase inhibitor miglitol increases hepatic CYP7A1 activity in association with altered short-chain fatty acid production in the gut of obese diabetic mice

Hamada, Yoji; Goto, Minoru; Nishimura, Go; Nagasaki, Hiroshi; Seino, Yusuke; Kawanishi, Hideki; Nakamura, Jiro

doi:10.1016/j.metop.2020.100024

Cited by 10 publications

(6 citation statements)

References 20 publications

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“…It is involved in the mechanism of reducing liver steatosis and blood lipids. 51 Some studies have found that the content of secondary bile acids in the hypothalamus of obese mice is significantly reduced. When a TGR5 agonist is given, the sympathetic nervous system is activated, which can reduce obesity and promote energy balance; 52 TGR5 is involved in the inhibition of dietary secondary bile acids in obesity.…”

Section: Discussionmentioning

confidence: 99%

Lingguizhugan Decoction Targets Intestinal Microbiota and Metabolites to Reduce Insulin Resistance in High-Fat Diet Rats

Ning¹,

Gong²,

Zheng³

et al. 2022

DMSO

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Background The increasing incidence of obesity and its complications has become a global public health problem. Lingguizhugan decoction (LGZGD) is a representative compound of traditional Chinese medicine (TCM) for metabolic diseases, such as nonalcoholic fatty liver disease, but its role in insulin resistance (IR) treatment is still less known. This study aims to evaluate the therapeutic properties of LGZGD on obesity-induced IR and explore the potential mechanism of LGZGD on gut microbiota and its metabolites in the treatment of IR. Methods In this study, we induced an IR model in the form of high-fat diet (HFD) rats gavaged with LGZGD (1.64 g/kg BW) for three weeks. The IR status was measured by biochemical assays and oral glucose tolerance tests. The degrees of damage to liver function and the intestinal barrier were observed by hematoxylin and eosin (H&E) staining and immunohistochemistry. Alterations in intestinal microbiota and metabolites were assessed by 16S rRNA and an untargeted metabolomics platform. Results Our results showed that after LGZGD treatment, the body weight, plasma insulin concentration and blood lipids were significantly decreased, and glucose tolerance and hepatic steatosis were ameliorated. In addition, small intestinal villi were restored, and the expression of Occludin was upregulated. The relative abundance of Akkermansia, Faecalibacterium and Phascolarctobacterium in the HFD-LGZG group was upregulated. Obesity-related metabolic pathways, such as bile secretion, biosynthesis of amino acids, phenylalanine metabolism, serotonergic synapse, protein digestion and absorption, taurine and hypotaurine metabolism, and primary bile acid biosynthesis, were changed. After LGZGD intervention, metabolites developed toward the healthy control group. In addition, the expression of bile acid metabolism related genes was also regulated in IR rats. Conclusion We showed that LGZGD relieved IR, possibly by regulating the composition of the fecal microbiota and its metabolites. The above studies provide a basis for further study of LGZGD in the treatment of IR and its clinical application.

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Section: Discussionmentioning

confidence: 99%

Lingguizhugan Decoction Targets Intestinal Microbiota and Metabolites to Reduce Insulin Resistance in High-Fat Diet Rats

Ning¹,

Gong²,

Zheng³

et al. 2022

DMSO

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“…Studies have discovered that increased SCFAs induce the upregulation of cytochrome p-450 enzyme cholesterol 7α-hydroxylase (CYP7A1) ( 70 ) and 27α-hydroxylase (CYP27A1) ( 71 ) in the liver. Upregulation of CYP7A1 promotes cholesterol converted into BAs ( 72 ), thereby increasing cholesterol consumption and lowering LDL-C levels.…”

Section: Points Of Contact Between Gut Microbiota and Cholesterol Met...mentioning

confidence: 99%

Targets of statins intervention in LDL-C metabolism: Gut microbiota

Sun

Wang

et al. 2022

Front. Cardiovasc. Med.

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Increasing researches have considered gut microbiota as a new “metabolic organ,” which mediates the occurrence and development of metabolic diseases. In addition, the liver is an important organ of lipid metabolism, and abnormal lipid metabolism can cause the elevation of blood lipids. Among them, elevated low-density lipoprotein cholesterol (LDL-C) is related with ectopic lipid deposition and metabolic diseases, and statins are widely used to lower LDL-C. In recent years, the gut microbiota has been shown to mediate statins efficacy, both in animals and humans. The effect of statins on microbiota abundance has been deeply explored, and the pathways through which statins reduce the LDL-C levels by affecting the abundance of microbiota have gradually been explored. In this review, we discussed the interaction between gut microbiota and cholesterol metabolism, especially the cholesterol-lowering effect of statins mediated by gut microbiota, via AMPK-PPARγ-SREBP1C/2, FXR and PXR-related, and LPS-TLR4-Myd88 pathways, which may help to explain the individual differences in statins efficacy.

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“…Existing studies have found that proteins that regulate lipid and glucose metabolism are significantly inhibited under diabetic settings, such as glucose transporter 2 (GLUT2), cholesterol 7 alpha-hydroxylase (CYP7A1), G-protein-coupled bile receptor (TGR5), and Farnesyl X receptor (FXR) [20,21]. To study the mechanism of TFA on bile acid metabolism, their protein expression was determined by western blot.…”

Section: Tfa Improved Glucose and Lipid Metabolism In The Liver Of Diabetic Micementioning

confidence: 99%

Total flavonoids of Astragalus Ameliorated Bile Acid Metabolism Dysfunction in Diabetes Mellitus

Wang

Hong

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Astragalus Radix is one of the common traditional Chinese medicines used to treat diabetes. However, the underlying mechanism is not fully understood. Flavones are a class of active components that have been reported to exert various activities. Existing evidence suggests that flavones from Astragalus Radix may be pivotal in modulating progression of diabetes. In this study, total flavones from Astragalus Radix (TFA) were studied to observe its effects on metabolism of bile acids both in vivo and in vitro. C57BL/6J mice were treated with STZ and high-fat feeding to construct diabetic model, and HepG2 cell line was applied to investigate the influence of TFA on liver cells. We found a serious disturbance of bile acids and lipid metabolism in diabetic mice, and oral administration or cell incubation with TFA significantly reduced the production of total cholesterol (TCHO), total triglyceride, glutamic oxalacetic transaminase (AST), glutamic-pyruvic transaminase (ALT), and low-density lipoprotein (LDL-C), while it increased the level of high-density lipoprotein (HDL-C). The expression of glucose transporter 2 (GLUT2) and cholesterol 7α-hydroxylase (CYP7A1) was significantly upregulated on TFA treatment, and FXR and TGR5 play pivotal role in modulating bile acid and lipid metabolism. This study supplied a novel understanding towards the mechanism of Astragalus Radix on controlling diabetes.

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The alpha-glucosidase inhibitor miglitol increases hepatic CYP7A1 activity in association with altered short-chain fatty acid production in the gut of obese diabetic mice

Cited by 10 publications

References 20 publications

Lingguizhugan Decoction Targets Intestinal Microbiota and Metabolites to Reduce Insulin Resistance in High-Fat Diet Rats

Lingguizhugan Decoction Targets Intestinal Microbiota and Metabolites to Reduce Insulin Resistance in High-Fat Diet Rats

Targets of statins intervention in LDL-C metabolism: Gut microbiota

Total flavonoids of Astragalus Ameliorated Bile Acid Metabolism Dysfunction in Diabetes Mellitus

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