Hyocholic Acid Species Improve Glucose Homeostasis Through a Distinct TGR5 and FXR Signaling Mechanism

Zheng, Xiaojiao; Chen, Tianlu; Jiang, Runqiu; Zhao, Aihua; Wu, Qing; Kuang, Junliang; Xia, Han; Li, Mengci; Wei, Meilin; Huang, Fengjie; Zhang, Yunjing; Wang, Shouli; Liang, Dandan; Bao, Yuqian; Dong, Bing; Li, Defa; Li, Huating; Hu, Cheng; Jia, Weiping; Wu, Jiayu; Xia, Jialin; Wang, Xuemei; Lan, Ke; Lyu, Aiping; Rajani, Cynthia; Xie, Guoxiang; Jiang, Changtao; Wang, Jia

doi:10.2139/ssrn.3528695

Cited by 26 publications

(36 citation statements)

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“…Analysis of clinical samples also showed that serum HCA was negatively correlated with diabetes and blood glucose levels. However, as the bile acids with less attention, HCA is expected to become potential therapeutic drugs for diabetes, and can also be combined with other hypoglycemic drugs to improve clinical efficacy ( Zheng et al, 2020 ). At the same time, because the metabolism of cholic acid is regulated by intestinal flora, how to improve the level of cholic acid in diabetic patients through intestinal flora will also become the focus of future research and drug development.…”

Section: Gm and Metabolic Diseasesmentioning

confidence: 99%

Role and Mechanism of Gut Microbiota in Human Disease

Chen

Zhou

Wang

2021

Front. Cell. Infect. Microbiol.

281

187

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The human gut microbiome is a huge microbial community that plays an irreplaceable role in human life. With the further development of research, the influence of intestinal flora on human diseases has been gradually excavated. Gut microbiota (GM) dysbiosis has adverse health effects on the human body that will lead to a variety of chronic diseases. The underlying mechanisms of GM on human diseases are incredibly complicated. This review focuses on the regulation and mechanism of GM on neurodegenerative diseases, cardiovascular diseases, metabolic diseases and gastrointestinal diseases, thus providing a potential target for the prevention and treatment of disease.

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Section: Gm and Metabolic Diseasesmentioning

confidence: 99%

Role and Mechanism of Gut Microbiota in Human Disease

Chen

Zhou

Wang

2021

Front. Cell. Infect. Microbiol.

281

187

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“…However, the FXR agonist GW4064 and CDCA (which preferentially binds FXR) were shown to suppress glucose-induced proglucagon expression and GLP-1 secretion in this cell line by decreasing glycolysis, whereas silencing FXR abolished these effects [ 27 ]. These observations have been replicated in studies with different L-cell lines (i.e., NCI-H736 [ 28 ] and STC-1 [ 29 ]). In a similar manner, GW4064 blunted the GLP-1 response to short-chain fatty acids (SCFA) in both GLUTag and NCI-H716 cell lines [ 30 ].…”

Section: Effects Of Bile Acids On Gastrointestinal Hormone Secretionmentioning

confidence: 66%

“…Consistent with these observations, FXR-deficient mice exhibited increased GLP-1 secretion in response to both dietary fiber, which increases colonic SCFA [ 30 ], and oral glucose [ 31 ]. Oral intake of GW4064 (10 mg/kg, 2 doses over 12 h) also decreased active GLP-1 levels in the plasma of mini-pigs [ 28 ]. However, in an isolated perfusion model of rat intestine, both luminal and vascular perfusion of GW4064 failed to affect the GLP-1 response to a physiological mixture of bile acids in rats [ 21 ].…”

Section: Effects Of Bile Acids On Gastrointestinal Hormone Secretionmentioning

confidence: 99%

“…For example, supplementation with CA or UDCA prevented weight gain in mice fed a high-fat diet [ 50 , 51 , 52 ], possibly reflecting a TGR5-related increase in energy expenditure [ 50 ]. Moreover, a number of other bile acid species with high affinity for TGR5 including hyocholic acid (HCA), hyodeoxycholic acid (HDCA), DCA, and TCA failed to affect energy intake or body weight in rodents with or without diabetes [ 28 , 53 , 54 ]. Information relating to the effects of bile acids on appetite and energy intake in humans are limited.…”

Section: Effects Of Bile Acid Signaling On Energy Intake and Body Weightmentioning

confidence: 99%

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Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease

et al. 2021

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Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

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“…The discovery of TβMCA and TωMCA in Common Carp was a break though since they were thought to be a rodent specific bile acid [38][39][40][41][42], and it not indeed be found in birds and monogastric animal BAs analysis [43,44], but which has also been found in humans by some reports [20,45]. Rodents branch off from fish in the evolutionary tree, and humans and rodents are on a small branch, we considered that MCA maybe a common specie of bile acids existed in fish, rodents, and primates.…”

Section: Bas Profile Changes Caused By Supplementary Of Basmentioning

confidence: 99%

Effects of Bile Acids Supplement in High Plant Protein Diet on Common Carp (Cyprinus Carpio) Bile Acids Profile and Hepatopancreas Health

Wang¹,

Yao²,

Fall³

et al. 2021

Preprint

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BackgroundBile acids (BAs) have considerable importance in the metabolism of glycolipid and cholesterol. BAs profile in mammals has been widely reported, but lacking in fishes. The purpose of the present study is to clarify BAs profiles of common carp and how exogenous additions of BAs could alleviate hepatopancreas injured of common carp under a high plant protein diet. A 11-week feeding trial was conducted with high plant protein diet (18%) (HP) and high plant protein diet (18%) added 600 mg/kg BAs (HP+BAs) for Common carp, and then the UHPLC-MS/MS technology was used to analyze the BAs in the bile and plasma of two groups. ResultsHP could induce vacuolation of hepatocytes and accumulation of glycogen in Common carp, while these phenotypes were significantly improved in HP+BAs group. In addition, BAs profile of HP group and HP+BAs group were described in detail, for Common carp bile with treatment by exogenous BAs, TCA, CA, T β MCA and T ω MCA were the main components. Furthermore, in HP+BAs group plasma, CDCA, CA, LCA, and GCDCA increased significantly, they could activate TGR5, the activation of hepatopancreas TGR5 might regulate glucose metabolism to relieve hepatopancreas glycogen accumulation. ConclusionsHP could induce glycogen accumulation in common carp hepatopancreas while supplemented BAs to HP could mitigate this symptom. And we determined that the reduction of common carp hepatopancreas glycogen accumulation in the HP+BAs group is importantly related to the change in the endogenous BAs profile after the addition of BAs in HP through an integrated bile acids profile determination by UHPLC-MS/MS . This study has important guiding significance for aquaculture.

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Hyocholic Acid Species Improve Glucose Homeostasis Through a Distinct TGR5 and FXR Signaling Mechanism

Cited by 26 publications

References 0 publications

Role and Mechanism of Gut Microbiota in Human Disease

Role and Mechanism of Gut Microbiota in Human Disease

Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease

Effects of Bile Acids Supplement in High Plant Protein Diet on Common Carp (Cyprinus Carpio) Bile Acids Profile and Hepatopancreas Health

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