title: Gallic acid ameliorated impaired glucose and lipid homeostasis in high fat diet-induced NAFLD mice.
abstract: Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more "holistic view" approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.
authors.affiliation: Institute of Pharmacology, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jung
authors.initials: J
authors.lastname: Chao
authors.affiliation: Institute of Pharmacology, College of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Oncology and Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
authors.affiliation: Department of Nursing, Chung Jen College of Nursing, Health Sciences and Management, Chia-Yi, Taiwan.
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Cheng
authors.affiliation: Department of Health and Nutrition Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Jiunn-Wang
authors.initials: JW
authors.lastname: Liao
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Meng-Shiou
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Qin
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Ming-Tsuen
authors.initials: MT
authors.lastname: Hsieh
authors.affiliation: Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Li-Heng
authors.initials: LH
authors.lastname: Pao
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Wen-Huang
authors.initials: WH
authors.lastname: Peng
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D005707:Gallic Acid / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006937:Hypercholesterolemia / Q000150:complications / Q000517:prevention & control; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000517:prevention & control
chemical_list: D005707:Gallic Acid; D005947:Glucose