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Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in 2 nonalcoholic steatohepatitis

ABSTRACT: In this study Guo et al. revealed an endocrine pathway regulated by skeletal muscle IRF4 that manipulates liver pathology. Mice with skeletal muscle specific ablation of IRF4 show ameliorated liver steatosis, inflammation, and fibrosis, without changes in body weight on nonalcoholic steatohepatitis (NASH) diet. Proteomics analysis of mouse serum suggested that follistatin-like protein 1 (FSTL1) might link the communication between muscle and liver. Dual luciferase assays showed that IRF4 could transcriptionally regulate FSTL1 and reconstitution of FSTL1 expression in muscle of F4MKO mice was sufficient to restore the liver pathology. Furthermore, co-culture experiments verified that FSTL1 exerts its function in hepatocyte, macrophage, and hepatic satellite cells through CD14 and DIP2A, CD14, DIP2A, respectively. In human, serum FSTL1 is increased in NASH patients, but the mRNA level of Fstl1 and its receptors are decreased in NASH liver biopsy, suggesting the increased serum FSTL1 is from skeletal muscle as studied in F4MKO mice. These data unveiled a signaling pathway from skeletal muscle to liver via IRF4-FSTL1-DIP2A/CD14 in the pathogenesis of NASH.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Serum

SUBMITTER: Yonghao Feng

LAB HEAD: Xingxing Kong

PROVIDER: PXD045324 | Pride | 2023-09-13

REPOSITORIES: Pride

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			Action	DRS
	KO1.csv	Csv
	KO1.raw	Raw
	KO2.csv	Csv
	KO2.raw	Raw
	KO3.csv	Csv

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Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in nonalcoholic steatohepatitis

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