Ahnak deficiency attenuates high-fat diet-induced fatty liver in mice through FGF21 induction

Yo Na Kim, Jae Hoon Shin, Dong Soo Kyeong, Soo Young Cho, Mi Young Kim, Hee Jung Lim, Maria Raquel Rojas Jimenez, Il Yong Kim, Mi Ock Lee, Yun Soo Bae, Je Kyung Seong

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The AHNAK nucleoprotein has been determined to exert an anti-obesity effect in adipose tissue and further inhibit adipogenic differentiation. In this study, we examined the role of AHNAK in regulating hepatic lipid metabolism to prevent diet-induced fatty liver. Ahnak KO mice have reportedly exhibited reduced fat accumulation in the liver and decreased serum triglyceride (TG) levels when provided with either a normal chow diet or a high-fat diet (HFD). Gene expression profiling was used to identify novel factors that could be modulated by genetic manipulation of the Ahnak gene. The results revealed that fibroblast growth factor 21 (FGF21) was markedly increased in the livers of Ahnak KO mice compared with WT mice fed a HFD. Ahnak knockdown in hepatocytes reportedly prevented excessive lipid accumulation induced by palmitate treatment and was associated with increased secretion of FGF21 and the expression of genes involved in fatty acid oxidation, which are primarily downstream of PPARα. These results indicate that pronounced obesity and hepatic steatosis are attenuated in HFD-fed Ahnak KO mice. This may be attributed, in part, to the induction of FGF21 and regulation of lipid metabolism, which are considered to be involved in increased fatty acid oxidation and reduced lipogenesis in the liver. These findings suggest that targeting AHNAK may have beneficial implications in preventing or treating hepatic steatosis.

Original languageEnglish
Pages (from-to)468-482
Number of pages15
JournalExperimental and Molecular Medicine
Volume53
Issue number3
DOIs
StatePublished - Mar 2021

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