Blueberry Extract Improves Obesity through Regulation of the Gut Microbiota and Bile Acids via Pathways Involving FXR and TGR5

Guo, Jielong; Han, Xue; Tan, Huan; Huang, Weidong; You, Yilin; Zhan, Jicheng

doi:10.1016/j.isci.2019.08.020

Cited by 90 publications

(108 citation statements)

References 35 publications

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“…Since the limited absorption and utilization of dietary polyphenols makes it difficult for polyphenols and metabolites in the blood to function, [ 16,26 ] many studies have shown that polyphenols exert anti‐obesity and anti‐inflammatory function through regulating GM. Grape seed proanthocyanidin extract (GSPE) ameliorated inflammation and adiposity in HFD mice.…”

Section: Discussionmentioning

confidence: 99%

“…The composition and concentration of the BAs in the plasma were determined through UPLC/electrospray ionization mass spectrometry (UPLC/ESI‐MS), as described previously with some modifications. [ 16 ] Briefly, 1 mL precooling ethanol was added to a 50 µL plasma sample, followed by vortexing and centrifugation. The supernatant was then filtered through a 0.22 µm filter before analysis.…”

Section: Methodsmentioning

confidence: 99%

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Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid

Han

Guo

Yin

et al. 2020

Molecular Nutrition Food Res

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Scope: Although the physiological function of grape extract (GE) has long been recognized, the precise mechanism remains obscure. This study is designed to investigate the effects of GE on metabolism and the association between GE activation of brown adipose tissue (BAT) and the restoration of gut microbiota (GM). Methods and results: Diet-induced obese mice are used to investigate the function of GE. GE administration increases energy metabolism and prevents obesity. Also, GE restores the dysbiosis of GM by augmenting the observed species, enhancing the Firmicutes-to-Bacteroidetes ratio and increasing the abundance of the Bifidobacteria, Akkermansia, and Clostridia genera. This restoration of GM alters the bile acid (BA) pool in the serum. The abundance of Akkermansia, Clostridium, and Bifidobacterium is negatively correlated with the concentrations of T MCA, T MCA, and TCA but is positively correlated with DCA. The changes in BA promoted TGR5 in BAT, which contributed to thermogenesis. The metabolites of GE in blood do not stimulate TGR5 in vitro. Conclusion: GE stimulates the thermogenesis of BAT through a pathway involving the regulation of GM and BA in diet-induced obese mice. This study reveals the mechanism by which dietary polyphenols promote thermogenesis by regulating BA, which is altered by GM. ments; X.H. wrote the paper.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid

Han

Guo

Yin

et al. 2020

Molecular Nutrition Food Res

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“…(2) Library preparation for transcriptome sequencing: A total amount of 3 μg RNA per sample was used as input material for the RNA sample preparations. Sequencing libraries were generated using the RNA Library Prep Kit for Illumina (NEB, USA) and index codes were added to attribute sequences to each sample, as previously described 26 . (3) Clustering and sequencing: The clustering of the index‐coded samples was performed on a cBot cluster generation system using TruSeq PE Cluster Kit v3‐cBot‐HS (Illumina).…”

Section: Methodsmentioning

confidence: 99%

p‐Coumaric acid prevents obesity via activating thermogenesis in brown adipose tissue mediated by mTORC1‐RPS6

et al. 2020

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Brown adipose tissue (BAT) has long been recognized as an energy‐consuming organ and a possible target for combating metabolism disorder. Although numerous studies have demonstrated the ability of phytochemical phenolic acids to improve obesity by activating BAT, the underlying mechanism or mechanism therein remain obscure. In this study, diet‐induced obese mice, genetically obese mice, and C3H10T1/2 cells were used to examine the effects of p‐Coumaric acid (CA) on metabolism profiles. The results showed that CA prevented metabolic syndromes in the two mice models through the activation of BAT. This phenomenon was closely linked to the upregulation of uncoupling protein 1 (UCP1) and the accelerated burning of fatty acids and glucose, which consequently enhanced the energy expenditure and thermogenesis. Similar results were also obtained in vitro. Importantly, these effects were mediated by the mammalian target of rapamycin complex 1 (mTORC1)‐RPS6 pathway. These findings reveal, to the best of our knowledge for the first time, the close correlation between mTORC1‐RPS6 and BAT‐mediated thermogenesis, and, in addition, the key role played by mTORC1‐RPS6 in mediating phenolic acids‐induced activation of BAT, thus preventing obesity.

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“…In our present study, metabolomics data showed that TUDCA in the intestinal contents of the HFD + Met group increased significantly. Previous studies revealed that metformin treatment increased the levels of the conjugated bile acid in the gut by decreasing the abundance of species of Bifidobacterium and its bile salt hydrolase (BSH) activity in the intestines of individuals with T2D 17,30,31 . Bile salt hydrolase, secreted by intestinal bacteria, decomposes TUDCA in the intestine and metabolizes TUDCA to taurine and UDCA.…”

Section: Discussionmentioning

confidence: 99%

“…Bile acids (BAs), which are produced in the liver and serve as important ingredients of the digestive fluid in the intestine, enter the small intestine through the biliary system and participate in fat digestion and absorption 15,16 . Gathered evidence demonstrates that BAs could improve the intestinal homeostasis by modulating the gut microbiota, thus relieving metabolic syndrome 17 . Recent studies also suggest that BAs can participate in the liver-gut axis circulation and the improvement of HFD-initiated metabolic disorders by inhibiting the proliferation of pathogenic bacteria 18,19 .…”

Section: Introductionmentioning

confidence: 99%

Metformin increases tauroursodeoxycholic acid levels to improve insulin resistance in diet-induced obese mice

Zhang

Zuo

Yan

et al. 2020

Preprint

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16Metformin is widely used to surmount insulin resistance (IR) and diabetes. 17 Evidence indicates that metformin remodels gut microbiota but the underlying 18 mechanism remain unclear. Present results showed that metformin effectively 19 improved insulin sensitivity and alleviated liver inflammation and oxidative stress in 20 30 improves metabolism. 31 NRF2 33 34 35The prevalence of obesity and overweight have been on the rise worldwide 1,2 . 36 Current predictions indicate that more than 1 billion people will be obese by 2030 3 . 37 Visceral obesity precedes the development of metabolic complications and chronic 38 diseases such as type 2 diabetes (T2D) 4 , hepatic steatosis 5 and cardiovascular 39 diseases 6 . Metformin has been the first-line anti-diabetic drug for more than 60 years 40 because of its excellent hypoglycemic effect and safety profile 1,7 . Although several 41 studies have explored the mechanisms by which metformin maintains glucose 42 homeostasis, findings from such studies are inconsistent. The prevailing view is that 43 metformin activates AMP-activated protein kinase (AMPK) in the liver, similar to the 44 principle of caloric restriction that relieves symptoms of diabetes 8,9 . However, 45 metformin is an orally administered drug that reaches high concentrations in the 46 intestine with much lower serum concentrations 10 , thus, the possibility that its 47 metabolic therapeutic mechanism might be due in part to actions in the intestine 48 cannot be ignored. Accumulated evidence shows that a high-fat diet (HFD) reduces 49 the abundance of Lactobacilli in the small intestine. However, this can be 50 counteracted by metformin, which increases the proportion of probiotics, thus, 51 relieving the symptoms of HFD-induced diabetes 11 . Although metformin may play a 52 hypoglycemic effect by improving the gut microbiota, oral administration of 53 antibiotics to diabetic mice impairs the hypoglycemic ability of metformin 12 . In 54 addition, while metformin can increase the abundance of Escherichia coli, it can as 55 well reduce the abundance of Intestinibacter. This can further influence diverse 56 biological processes such as the synthesis of branched-chain amino acid and the 57 secretion of GPL-1, thereby improving glucose tolerance and alleviating insulin 58 resistance (IR) 13,14 . These findings suggest that modulation of gut microbiota is 59 involved in the hypoglycemic mechanism of metformin. 60 Bile acids (BAs), which are produced in the liver and serve as important 61 ingredients of the digestive fluid in the intestine, enter the small intestine through the 62 biliary system and participate in fat digestion and absorption 15,16 . Gathered evidence 63 demonstrates that BAs could improve the intestinal homeostasis by modulating the 64 gut microbiota, thus relieving metabolic syndrome 17 . Recent studies also suggest that 65 BAs can participate in the liver-gut axis circulation and the improvement of 66 HFD-initiated metabolic disorders by inhibiting the proliferation of path...

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Blueberry Extract Improves Obesity through Regulation of the Gut Microbiota and Bile Acids via Pathways Involving FXR and TGR5

Cited by 90 publications

References 35 publications

Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid

Grape Extract Activates Brown Adipose Tissue Through Pathway Involving the Regulation of Gut Microbiota and Bile Acid

p‐Coumaric acid prevents obesity via activating thermogenesis in brown adipose tissue mediated by mTORC1‐RPS6

Metformin increases tauroursodeoxycholic acid levels to improve insulin resistance in diet-induced obese mice

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