Gallic Acid Regulates Body Weight and Glucose Homeostasis Through AMPK Activation

被引：146

作者：

Doan, Khanh V. ^{[1
,2
,3
,4
]}

Ko, Chang Mann ^{[1
,2
]}

Kinyua, Ann W. ^{[1
,2
]}

Yang, Dong Joo ^{[1
,2
,3
,4
]}

Choi, Yun-Hee ^{[1
,2
,3
,4
,10
]}

Oh, In Young ^{[1
,2
]}

Nguyen Minh Nguyen ^{[1
,2
]}

Ko, Ara ^{[1
,2
]}

Choi, Jae Won ^{[1
,2
]}

Jeong, Yangsik ^{[5
]}

Jung, Min Ho ^{[6
]}

Cho, Won Gil ^{[6
]}

Xu, Shanhua ^{[7
]}

Park, Kyu Sang ^{[7
]}

Park, Woo Jin ^{[8
]}

Choi, Soo Yong ^{[9
]}

Kim, Hyoung Shik ^{[10
]}

Moh, Sang Hyun ^{[10
]}

Kim, Ki Woo ^{[1
,2
,3
,4
]}

机构：

[1] Yonsei Univ, Coll Med, Dept Pharmacol, Wonju 220701, South Korea

[2] Yonsei Univ, Coll Med, Dept Global Med Sci, Wonju 220701, South Korea

[3] Yonsei Univ, Coll Med, Inst Lifestyle Med, Wonju 220701, South Korea

[4] Yonsei Univ, Coll Med, Nucl Receptor Res Consortium, Wonju 220701, South Korea

[5] Yonsei Univ, Coll Med, Dept Biochem, Wonju 220701, South Korea

[6] Yonsei Univ, Coll Med, Dept Anat, Wonju 220701, South Korea

[7] Yonsei Univ, Coll Med, Dept Physiol, Wonju 220701, South Korea

[8] Gwangju Inst Sci & Technol, Global Res Lab, Kwangju 500757, South Korea

[9] Innoplant Co Ltd, Gyeongnam 660844, South Korea

[10] Antiaging Res Inst BIO FD & C Co Ltd, Inchon 406840, South Korea

来源：

ENDOCRINOLOGY | 2015年 / 156卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

DIET-INDUCED OBESITY; PROTEIN-KINASE; ENERGY-EXPENDITURE; SKELETAL-MUSCLE; HEPATIC GLUCONEOGENESIS; MITOCHONDRIAL-FUNCTION; DIRECT PHOSPHORYLATION; LIPID-METABOLISM; THYROID-HORMONE; GREEN TEA;

D O I：

10.1210/en.2014-1354

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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 which GA exerts its beneficial effects is not known. Here we report that GA plays its role through the activation of AMP-activated protein kinase (AMPK) and by regulating mitochondrial function via the activation of peroxisome proliferator-activated receptor-gamma coactivator1 alpha (PGC1 alpha). Sirtuin 1 (Sirt1) knockdown significantly blunted GA's effect on PGC1 alpha activation and downstream genes, suggesting a critical role of the AMPK/Sirt1/PGC1 alpha pathway in GA's action. Moreover, diet-induced 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/PGC1 alpha 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/PGC1 alpha pathway by GA or its derivatives might be a potential therapeutic intervention for insulin resistance in metabolic diseases.

引用

页码：157 / 168

页数：12

共 55 条

[1]

Gallic acid improves glucose tolerance and triglyceride concentration in diet-induced obesity mice [J].