Chenodeoxycholic acid attenuates high‑fat diet‑induced obesity and hyperglycemia via the G protein‑coupled bile acid receptor 1 and proliferator‑activated receptor γ pathway

Chen,Xiaosong; Yan,Liu; Guo,Zhihui; Chen,Ying; Li,Ming; Huang,Chushan; Chen,Zhaohong; Meng,Xiyong

doi:10.3892/etm.2017.5232

Chenodeoxycholic acid attenuates high‑fat diet‑induced obesity and hyperglycemia via the G protein‑coupled bile acid receptor 1 and proliferator‑activated receptor γ pathway

Authors:
- Xiaosong Chen
- Liu Yan
- Zhihui Guo
- Ying Chen
- Ming Li
- Chushan Huang
- Zhaohong Chen
- Xiyong Meng
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Affiliations: Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Burns Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Plastic Surgery, No. 421 Hospital of Chinese PLA, Guangzhou, Guangdong 510318, P.R. China
Published online on: September 29, 2017 https://doi.org/10.3892/etm.2017.5232
Pages: 5305-5312
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

G protein‑coupled bile acid receptor 1 (TGR5) serves a key function in regulating glycometabolism. TGR5 is highly expressed in the mitochondria of brown adipose tissue (BAT) and downregulates adenosine triphosphate synthesis via the bile acid‑TGR5‑cyclic adenosine monophosphate‑2‑iodothyronine deiodinase (D2)‑triiodothyronine‑uncoupling protein pathway, thus regulating energy homeostasis and reducing body weight. Chenodeoxycholic acid (CDCA), the primary bile acid, is a natural ligand of TGR5. The present study aimed to characterize the ability of CDCA to reduce high‑fat diet‑induced obesity and improve glucose tolerance. A mouse model of diet‑induced obesity was constructed. The results demonstrated that a high‑fat diet significantly increased the weight of mice after 10 weeks (P<0.05), but following the addition of CDCA and continued feeding for another 10 weeks, a decrease in weight was detected and no significant difference in final weight was observed between the high fat diet group treated with CDCA and the group fed a normal diet. Furthermore, CDCA treatment significantly increased glucose tolerance (P<0.001, P<0.01 and P<0.01 at 15, 40 and 60 min after glucose injection, respectively) and significantly decreased serum insulin levels compared with mice fed a high‑fat diet alone. Staining of the liver with hematoxylin and eosin and oil red O revealed that the CDCA‑treated group exhibited significantly lower fat accumulation in BAT and WAT compared with mice fed a high‑fat diet alone (P<0.001). Reverse transcription‑quantitative polymerase chain reaction analysis demonstrated that the expression of D2 activation system‑related factors was significantly increased in BAT from mice treated with CDCA (P<0.001), confirming the role of TGR5 in modulating high‑fat diet‑induced obesity. In addition, CDCA inhibited adipocyte differentiation in 3T3‑L1 cells and inhibited ligand‑stimulated peroxisome proliferator‑activated receptor γ (PPARγ) transcriptional activity. These results suggest that CDCA may prevent high‑fat diet‑induced obesity and hyperglycemia, and that these beneficial effects are mediated via the activation of TGR5 and inhibition of PPARγ transcriptional activity.

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