SNRK Modulates MTOR-autophagy Pathway for Liver Lipid Homeostasis in MAFLD

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2024 Nov 10

PMID 39521960

Authors

Shan Lin

Xiusheng Qiu

Xiaoying Fu

Shuting Zhang

Changyong Tang

Jian Kuang

Haixia Guan

Shuiqing Lai

Affiliations

Soon will be listed here.

Abstract

Metabolism-related fatty liver disease (MAFLD) is associated with abnormal fat accumulation in the liver. The exact mechanism underlying the occurrence and development of MAFLD remains to be elucidated. Here, we discovered that the expression of sucrose non-fermenting-related kinase (SNRK) is elevated in the liver of the MAFLD population. Mice deficient in SNRK exhibited damage to fatty acid oxidation and persistent accumulation of lipids in the liver. Pharmacological inhibition of the mTOR pathway in SNRK-deficient mice restored autophagy and improved lipid accumulation. In terms of mechanism, we observed that SNRK binds to the raptor component of mTOR complex 1, promoting fatty acid oxidation in the liver by activating autophagy. Overexpression of SNRK in high-fat diet-induced obese mice restored autophagy and ameliorated lipid accumulation. Notably, we also demonstrated that overexpression of SNRK significantly enhanced fatty acid oxidation in the mouse liver. We further confirmed that SNRK is essential for the liver to regulate autophagy and fatty acid oxidation. These findings underscore the importance of the potential of SNRK in the treatment of MAFLD.

Citing Articles

SNRK tames mTOR against metabolic dysfunction-associated steatotic liver disease.

Brunetti-Pierri N, Bewersdorf L, Strnad P Mol Ther. 2024; 33(1):28-29.

PMID: 39729984 PMC: 11764957. DOI: 10.1016/j.ymthe.2024.12.031.

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