title: Gallic Acid, the Active Ingredient of Terminalia bellirica, Enhances Adipocyte Differentiation and Adiponectin Secretion.
abstract: Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10-30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Makihara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Koike
authors.forename: Masatomi
authors.initials: M
authors.lastname: Ohta
authors.forename: Emi
authors.initials: E
authors.lastname: Horiguchi-Babamoto
authors.forename: Masahito
authors.initials: M
authors.lastname: Tsubata
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Tomoko
authors.initials: T
authors.lastname: Akase
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.forename: Masaki
authors.initials: M
authors.lastname: Aburada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005638:Fruit; D005707:Gallic Acid / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D029766:Terminalia; D014280:Triglycerides / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D047495:PPAR gamma; D010936:Plant Extracts; D014280:Triglycerides; D005707:Gallic Acid