TGR5, Not Only a Metabolic Regulator

Guo, Cong; Chen, Weidong; Wang, Yan Dong

doi:10.3389/fphys.2016.00646

Cited by 184 publications

(144 citation statements)

References 87 publications

(124 reference statements)

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“…study, because EGCG increased the expression of Tgr5 and the concentration of TGR-5 agonists (i.e., TLCA and LCA), it is likely that EGCG activates TGR-5 and its associated signaling. This notion is also supported by the findings that EGCG increased the expression of TGR-5 target genes, including Dio2 and Nos1 (39). Moreover, consistent with our data that showed that WD-fed mice had reduced Dio2 in their visceral fat and ileum, patients with obesity also have reduced DIO-2 in their white adipose tissues (67).…”

Section: Discussionsupporting

confidence: 91%

“…Because of the significant change in BAs in the cecal content in response to EGCG supplementation, we studied TGR-5 and FXR signaling in different tissues. TGR-5induced Dio2 potentially can improve metabolism by generating thyroxine (39). In the liver, visceral fat, and ileum, WD intake reduced Tgr5 and Dio2 mRNA levels with the exception of ileal Tgr5.…”

Section: Egcg Regulates Tgr-5 and Fxr-mediated Signaling Pathwaysmentioning

confidence: 99%

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Obesity treatment by epigallocatechin‐3‐gallate−regulated bile acid signaling and its enriched Akkermansia muciniphila

et al. 2018

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Dysregulated bile acid (BA) synthesis is accompanied by dysbiosis, leading to compromised metabolism. This study analyzes the effect of epigallocatechin-3-gallate (EGCG) on diet-induced obesity through regulation of BA signaling and gut microbiota. The data revealed that EGCG effectively reduced diet-increased obesity, visceral fat, and insulin resistance. Gene profiling data showed that EGCG had a significant impact on regulating genes implicated in fatty acid uptake, adipogenesis, and metabolism in the adipose tissue. In addition, metabolomics analysis revealed that EGCG altered the lipid and sugar metabolic pathways. In the intestine, EGCG reduced the FXR agonist chenodeoxycholic acid, as well as the FXR-regulated pathway, suggesting intestinal FXR deactivation. However, in the liver, EGCG increased the concentration of FXR and TGR-5 agonists and their regulated signaling. Furthermore, our data suggested that EGCG activated Takeda G protein receptor (TGR)-5 based on increased GLP-1 release and elevated serum PYY level. EGCG and antibiotics had distinct antibacterial effects. They also differentially altered body weight and BA composition. EGCG, but not antibiotics, increased Verrucomicrobiaceae, under which EGCG promoted intestinal bloom of Akkermansia muciniphila. Excitingly, A. muciniphila was as effective as EGCG in treating diet-induced obesity. Together, EGCG shifts gut microbiota and regulates BA signaling thereby having a metabolic beneficial effect.-Sheng, L., Jena, P. K., Liu, H.-X., Hu, Y., Nagar, N., Bronner, D. N., Settles, M. L., Bäumler, A. J. Wan, Y.-J. Y. Obesity treatment by epigallocatechin-3-gallate-regulated bile acid signaling and its enriched Akkermansia muciniphila.

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Section: Discussionsupporting

confidence: 91%

Section: Egcg Regulates Tgr-5 and Fxr-mediated Signaling Pathwaysmentioning

confidence: 99%

Obesity treatment by epigallocatechin‐3‐gallate−regulated bile acid signaling and its enriched Akkermansia muciniphila

et al. 2018

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“…To monitor TGR5 activity, we studied the expression of the Tgr5 gene as well as its downstream target. Activation of TGR5 induces type II iodothyronine deiodinase (Dio2) that generates thyroxine, a key player in basal metabolism [33]. In addition, BA-activated TGR5 stimulates nitric oxide production by inducing Nos3 in vascular endothelial cells [34].…”

Section: Effect Of Diet and Dermatitis Development On Tgr5 Signalingmentioning

confidence: 99%

Long-term Western diet intake leads to dysregulated bile acid signaling and dermatitis with Th2 and Th17 pathway features in mice

Jena

Sheng

McNeil

et al. 2019

Journal of Dermatological Science

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Background: Dietary interventions are implicated in the development of atopic dermatitis, psoriasis, and acne. Objective: To investigate the effect of diet and the bile acid (BA) receptors, such as TGR5 (Takeda G protein receptor 5) and S1PR2 (sphingosine-1-phosphate receptor 2) in the development of dermatitis. Methods: C57BL/6 mice were fed a control diet (CD) or Western diet (WD) since weaning until they were 10 months old followed by analyzing histology, gene expression, and BA profiling. Results: Mice developed dermatitis as they aged and the incidence was higher in females than males. Additionally, WD intake substantially increased the incidence of dermatitis. Cutaneous antimicrobial peptide genesS100A8, S100A9, and Defb4 were reduced in WD-fed mice, but increased when mice developed skin lesions. In addition, Tgr5 and TGR5-regulated Dio2 and Nos3 were reduced in WD intake but induced in dermatitic lesions. Trpa1 and Trpv1, which mediate itch, were also increased in dermatitic lesions. The expression of S1pr2 and genes encoding sphingosine kinases, S1P phosphatases, binding protein, and transporter were all reduced by WD intake but elevated in dermatitic lesions. Furthermore, dermatitis development increased total cutaneous BA with an altered profile, which may change TGR5 and S1PR2 activity. Moreover, supplementation with BA sequestrant cholestyramine reduced epidermal thickening as well as cutaneous inflammatory cytokines. Conclusion: In summary, activation of TGR5 and S1PR2, which regulate itch, keratinocyte proliferation, metabolism, and inflammation, may contribute to WD-exacerbated dermatitis with Th2 and Th17 features. In addition, elevated total BA play a significant role in inducing dermatitis and cutaneous inflammation.

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“…TGR5 activation leads to an increase in cAMP and PKA activation and has been shown to modulate bile acid homeostasis and inflammation (49–51). TGR5 has been detected in cholangiocytes, Kupffer cells, and sinusoidal endothelial cells but not hepatocytes (52).…”

Section: The Response Of Cholangiocytes To Cholestasismentioning

confidence: 99%

Mechanisms of bile acid mediated inflammation in the liver

Cai

Boyer

2017

Molecular Aspects of Medicine

206

120

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Bile acids are synthesized in the liver and are the major component in bile. Impaired bile flow leads to cholestasis that is characterized by elevated levels of bile acid in the liver and serum, followed by hepatocyte and biliary injury. Although the causes of cholestasis have been extensively studied, the molecular mechanisms as to how bile acids initiate liver injury remain controversial. In this chapter, we summarize recent advances in the pathogenesis of bile acid induced liver injury. These include bile acid signaling pathways in hepatocytes as well as the response of cholangiocytes and innate immune cells in the liver in both patients with cholestasis and cholestatic animal models. We focus on how bile acids trigger the production of molecular mediators of neutrophil recruitment and the role of the inflammatory response in this pathological process. These advances point to a number of novel targets where drugs might be judged to be effective therapies for cholestatic liver injury.

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TGR5, Not Only a Metabolic Regulator

Cited by 184 publications

References 87 publications

Obesity treatment by epigallocatechin‐3‐gallate−regulated bile acid signaling and its enriched Akkermansia muciniphila

Obesity treatment by epigallocatechin‐3‐gallate−regulated bile acid signaling and its enriched Akkermansia muciniphila

Long-term Western diet intake leads to dysregulated bile acid signaling and dermatitis with Th2 and Th17 pathway features in mice

Mechanisms of bile acid mediated inflammation in the liver

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