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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
  • View Affiliations / Copyright

    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
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5305-5312
    |
    Published online on: September 29, 2017
       https://doi.org/10.3892/etm.2017.5232
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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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Copy and paste a formatted citation
Spandidos Publications style
Chen X, Yan L, Guo Z, Chen Y, Li M, Huang C, Chen Z and Meng X: 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. Exp Ther Med 14: 5305-5312, 2017.
APA
Chen, X., Yan, L., Guo, Z., Chen, Y., Li, M., Huang, C. ... Meng, X. (2017). 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. Experimental and Therapeutic Medicine, 14, 5305-5312. https://doi.org/10.3892/etm.2017.5232
MLA
Chen, X., Yan, L., Guo, Z., Chen, Y., Li, M., Huang, C., Chen, Z., Meng, X."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". Experimental and Therapeutic Medicine 14.6 (2017): 5305-5312.
Chicago
Chen, X., Yan, L., Guo, Z., Chen, Y., Li, M., Huang, C., Chen, Z., Meng, X."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". Experimental and Therapeutic Medicine 14, no. 6 (2017): 5305-5312. https://doi.org/10.3892/etm.2017.5232
Copy and paste a formatted citation
x
Spandidos Publications style
Chen X, Yan L, Guo Z, Chen Y, Li M, Huang C, Chen Z and Meng X: 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. Exp Ther Med 14: 5305-5312, 2017.
APA
Chen, X., Yan, L., Guo, Z., Chen, Y., Li, M., Huang, C. ... Meng, X. (2017). 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. Experimental and Therapeutic Medicine, 14, 5305-5312. https://doi.org/10.3892/etm.2017.5232
MLA
Chen, X., Yan, L., Guo, Z., Chen, Y., Li, M., Huang, C., Chen, Z., Meng, X."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". Experimental and Therapeutic Medicine 14.6 (2017): 5305-5312.
Chicago
Chen, X., Yan, L., Guo, Z., Chen, Y., Li, M., Huang, C., Chen, Z., Meng, X."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". Experimental and Therapeutic Medicine 14, no. 6 (2017): 5305-5312. https://doi.org/10.3892/etm.2017.5232
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