2. Academic Validation
  3. Meteorin-like alleviates hepatic steatosis by regulating hepatic triglyceride secretion and fatty acid oxidation

Meteorin-like alleviates hepatic steatosis by regulating hepatic triglyceride secretion and fatty acid oxidation

  • Cell Rep. 2025 Feb 25;44(2):115246. doi: 10.1016/j.celrep.2025.115246.
Lingyu Song 1,  Yali Huang 1,  Lu Liu 1,  Xuebing Chang 1,  Laying Hu 1,  Guifang Wang 1,  Lifen Xu 2,  Tian Zhang 1,  Yuanyuan Wang 1,  Ying Xiao 1,  Hong Yang 1,  Suye Ran 1,  Qing Shi 1,  Tuanlao Wang 3,  Mingjun Shi 4,  Yuxia Zhou 5,  Bing Guo 6
Affiliations

Affiliations

  • 1 Department of Pathophysiology, and Department of Gastroenterology of the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Gui'an New Area, 561113, China.
  • 2 Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou, China.
  • 3 School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, 361005, Fujian, China.
  • 4 Department of Pathophysiology, and Department of Gastroenterology of the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Gui'an New Area, 561113, China. Electronic address: smjtyf@126.com.
  • 5 Department of Pathophysiology, and Department of Gastroenterology of the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Gui'an New Area, 561113, China. Electronic address: zhouyuxia_27@163.com.
  • 6 Department of Pathophysiology, and Department of Gastroenterology of the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Gui'an New Area, 561113, China; Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases and Guizhou Province Talent Base of Research on the Pathogenesis and Drug Prevention and Treatment for Common Major Diseases, Guizhou Medical University, Gui'an New Area, 561113, China; Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University, Gui'an New Area, 561113, Guizhou, China. Electronic address: guobingbs@126.com.
PMID: 39918960 DOI: 10.1016/j.celrep.2025.115246
Abstract

Amid a rising prevalence of non-alcoholic fatty liver disease (NAFLD), there is still an unmet need to better treat it. We identified a secreted factor, Meteorin-like (Metrnl), with decreased levels in livers with hepatic steatosis. Notably, recombinant Metrnl ameliorated hepatic steatosis in NAFLD mouse models. Mechanistically, Metrnl exerted dual effects by promoting triglyceride (TG) transportation by the phosphatidylinositol 3-kinase (PI3K)/Akt/Sp1/cytidylyltransferase α (CCTα) axis, thereby increasing the biosynthesis of phosphatidylcholine (PC) to facilitate TG secretion from the liver while facilitating AMP-activated protein kinase (AMPK)-dependent fatty acid oxidation (FAO). Exogenous injection of cytidine diphosphocholine (CDP)-choline, the production of CCTα, to increase PC synthesis, was shown to restore the inhibition of TG secretion in hepatic Metrnl-deficient (LKO-Met) mice. Combining CDP-choline and an AMPK Activator was sufficient to rescue hepatic steatosis in LKO-Met mice. Collectively, these findings reveal unexpected roles of Metrnl as a factor in PC biosynthesis, TG secretion, and FAO, suggesting potential therapeutic application for NAFLD.

Keywords

Akt; CP: Cell biology; FAO; Meteorin-like; Metrnl; NAFLD; PC; VLDL; fatty acid oxidation; non-alcoholic fatty liver disease; phosphatidylcholine; steatosis; very-low-density lipoprotein.

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