title: Gallic acid regulates body weight and glucose homeostasis through AMPK activation.
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 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-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, 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/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.
authors.affiliation: Departments of Pharmacology and Global Medical Science (K.V.D., C.M.K., A.W.K., D.J.Y., Y.-H.C., I.Y.O., N.M.N., A.K., J.W.C., K.W.K.), Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium (D.V.K., D.J.Y., Y.-H.C., K.W.K.), and Departments of Biochemistry (Y.J.), Anatomy (M.H.J., W.G.C.), and Physiology (S.X., K.S.P.), Yonsei University Wonju College of Medicine, Wonju 220-701, Republic of Korea; Global Research Laboratory (W.J.P.), Gwangju Institute of Science and Technology, Gwangju 500-757, Republic of Korea; Innoplant Co, Ltd (S.Y.C.), Jinju, Gyeongnam 660-844, Republic of Korea; and Antiaging Research Institute of BIO-FD & C Co Ltd (H.S.K., S.H.M., Y.-H.C.), Incheon 406-840, Republic of Korea.
authors.forename: Khanh V
authors.initials: KV
authors.lastname: Doan
authors.forename: Chang Mann
authors.initials: CM
authors.lastname: Ko
authors.forename: Ann W
authors.initials: AW
authors.lastname: Kinyua
authors.forename: Dong Joo
authors.initials: DJ
authors.lastname: Yang
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Choi
authors.forename: In Young
authors.initials: IY
authors.lastname: Oh
authors.forename: Nguyen Minh
authors.initials: NM
authors.lastname: Nguyen
authors.forename: Ara
authors.initials: A
authors.lastname: Ko
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Choi
authors.forename: Yangsik
authors.initials: Y
authors.lastname: Jeong
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Jung
authors.forename: Won Gil
authors.initials: WG
authors.lastname: Cho
authors.forename: Shanhua
authors.initials: S
authors.lastname: Xu
authors.forename: Kyu Sang
authors.initials: KS
authors.lastname: Park
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Park
authors.forename: Soo Yong
authors.initials: SY
authors.lastname: Choi
authors.forename: Hyoung Shik
authors.initials: HS
authors.lastname: Kim
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Moh
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D001786:Blood Glucose; D001835:Body Weight / Q000502:physiology*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004789:Enzyme Activation; D005707:Gallic Acid / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D014157:Transcription Factors; D005707:Gallic Acid; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1; D005947:Glucose