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(-)-Hydroxycitric Acid Alleviates Oleic Acid-Induced Steatosis, Oxidative Stress, and Inflammation in Primary Chicken Hepatocytes by Regulating AMP-Activated Protein Kinase-Mediated Reactive Oxygen Species Levels.

Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most complex liver diseases in the world, which is characterized by hepatic steatosis, oxidative stress, inflammation, and apoptosis. (-)-Hydroxycitric acid [(-)-HCA] can regulate obesity in different animals, while whether this beneficial effect of (-)-HCA can alleviate the NAFLD and its mechanism is unclear. Hence, this study aimed to determine the potential actions and mechanisms of (-)-HCA on NAFLD in oleic acid (OA)-induced hepatocytes. We found that (-)-HCA effectively improved OA-induced hepatic steatosis by regulating the expression level of fat metabolism key factors, which was achieved by activating AMP-activated protein kinase (AMPK) signaling in hepatocytes. Importantly, activated AMPK alleviates mitochondrial disorder via the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)-nuclear transcription factor 1 (NRF-1)-mitochondrial transcription factor A (TFAM) pathway, then reduces reactive oxygen species production, and blocks the activation of p38 MAPK-NF-κB pathway in OA-induced hepatocytes. These results not only provide a theoretical basis for the occurrence and development of NAFLD but also offer compelling evidence for prevention of NAFLD supplemental with (-)-HCA.
AuthorsLonglong Li, Xu Chu, Yao Yao, Ji Cao, Qian Li, Haitian Ma
JournalJournal of agricultural and food chemistry (J Agric Food Chem) Vol. 68 Issue 40 Pg. 11229-11241 (Oct 07 2020) ISSN: 1520-5118 [Electronic] United States
PMID32940033 (Publication Type: Journal Article)
Chemical References
  • Citrates
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Reactive Oxygen Species
  • Oleic Acid
  • hydroxycitric acid
  • AMP-Activated Protein Kinases
Topics
  • AMP-Activated Protein Kinases (genetics, metabolism)
  • Animals
  • Chickens
  • Citrates (pharmacology)
  • Hepatocytes (drug effects, metabolism)
  • Non-alcoholic Fatty Liver Disease (chemically induced, drug therapy, genetics, metabolism)
  • Oleic Acid (adverse effects)
  • Oxidative Stress (drug effects)
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (genetics, metabolism)
  • Reactive Oxygen Species (metabolism)

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