2. Academic Validation
  3. Exposure to Succinate Leads to Steatosis in Non-Obese Non-Alcoholic Fatty Liver Disease by Inhibiting AMPK/PPARα/FGF21-Dependent Fatty Acid Oxidation

Exposure to Succinate Leads to Steatosis in Non-Obese Non-Alcoholic Fatty Liver Disease by Inhibiting AMPK/PPARα/FGF21-Dependent Fatty Acid Oxidation

  • J Agric Food Chem. 2024 Sep 25;72(38):21052-21064. doi: 10.1021/acs.jafc.4c05671.
Hong Yang 1,  Suye Ran 2,  Yuxia Zhou 3,  Qing Shi 2,  Jiangnan Yu 4,  Wenjuan Wang 5,  Chengqin Sun 2,  Dengke Li 6,  Yue Hu 1,  Chen Pan 1,  Qi Yuan 1,  Yunhuan Zhen 7,  Qi Liu 1,  Lingyu Song 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, China.
  • 2 Guizhou Medical University, Guiyang, Guizhou 550025, China.
  • 3 Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou 550025, China.
  • 4 Department of Gastroenterology, Guizhou Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guiyang, Guizhou 550000, China.
  • 5 Department of Gastroenterology, Xingyi People's Hospital, Xingyi, Guizhou 562400, China.
  • 6 Luoyang Vocational and Technical College, Luoyang, Henan 471000, China.
  • 7 Department of Colorectal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, China.
PMID: 39268842 DOI: 10.1021/acs.jafc.4c05671
Abstract

Succinate is an important metabolite and a critical chemical with diverse applications in the food, pharmaceutical, and agriculture industries. Recent studies have demonstrated several protective or detrimental functions of succinate in diseases; however, the effect of succinate on lipid metabolism is still unclear. Here, we identified a role of succinate in nonobese nonalcoholic fatty liver disease (NAFLD). Specifically, the level of succinate is increased in the livers and serum of mice with hepatic steatosis. The administration of succinate promotes triglyceride (TG) deposition and hepatic steatosis by suppressing fatty acid oxidation (FAO) in nonobese NAFLD mouse models. RNA-Seq revealed that succinate suppressed Fibroblast Growth Factor 21 (FGF21) expression. Then, the restoration of FGF21 was sufficient to alleviate hepatic steatosis and FAO inhibition induced by succinate treatment in vitro and in vivo. Furthermore, the inhibition of FGF21 expression and FAO mediated by succinate was dependent on the AMPK/PPARα axis. This study provides evidence linking succinate exposure to abnormal hepatic lipid metabolism and the progression of nonobese NAFLD.

Keywords

AMPK; PPARα; fatty acid oxidation; nonobese NAFLD; succinate.

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