Gallic acid regulates body weight and glucose homeostasis through AMPK activation

Khanh V. Doan, Chang Mann Ko, Ann W. Kinyua, Dong Joo Yang, Yun Hee Choi, In Young Oh, Nguyen Minh Nguyen, Ara Ko, Jae Won Choi, Yangsik Jeong, Min Ho Jung, Won Gil Cho, Shanhua Xu, Kyu Sang Park, Woo Jin Park, Soo Yong Choi, Hyoung Shik Kim, Sang Hyun Moh, Ki Woo Kim

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Abstract

Gallic acid [3,4,5-trihydroxybenzoic acid (GA)], a natural phytochemical, is known to have a variety of cellular functions including beneficial effects on metabolic syndromes. However, the molecular mechanism by whichGAexerts its beneficial effects is not known. Herewereport thatGAplays its role through the activation of AMP-Activated protein kinase (AMPK) and by regulating mitochondrial function via the activation of peroxisome proliferator-Activated receptor-γ coactivator1α (PGC1α). Sirtuin 1 (Sirt1) knockdown significantly blunted GA's effect on PGC1α activation and downstream genes, suggesting a critical role of the AMPK/Sirt1/PGC1α pathway in GA's action. Moreover, dietinduced obese mice treated with GA showed significantly improved glucose and insulin homeostasis. In addition, the administration of GA protected diet-induced body weight gain without a change in food intake. Biochemical analyses revealed a marked activation of AMPK in the liver, muscle, and interscapular brown adipose tissue of the GA-treated mice. Moreover, uncoupling protein 1 together with other genes related to energy expenditure was significantly elevated in the interscapular brown adipose tissue. Taken together, these results indicate that GA plays its beneficial metabolic roles by activating the AMPK/Sirt1/PGC1α pathway and by changing the interscapular brown adipose tissue genes related to thermogenesis. Our study points out that targeting the activation of the AMPK/Sirt1/PGC1α pathway by GA or its derivatives might be a potential therapeutic intervention for insulin resistance in metabolic diseases.

Original languageEnglish
Pages (from-to)157-168
Number of pages12
JournalEndocrinology
Volume156
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

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All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Doan, K. V., Ko, C. M., Kinyua, A. W., Yang, D. J., Choi, Y. H., Oh, I. Y., Nguyen, N. M., Ko, A., Choi, J. W., Jeong, Y., Jung, M. H., Cho, W. G., Xu, S., Park, K. S., Park, W. J., Choi, S. Y., Kim, H. S., Moh, S. H., & Kim, K. W. (2015). Gallic acid regulates body weight and glucose homeostasis through AMPK activation. Endocrinology, 156(1), 157-168. https://doi.org/10.1210/en.2014-1354