Fat-specific protein 27b is regulated by hepatic peroxisome proliferator-activated receptor γ in hepatic steatosis

Abstract

The fat-specific protein 27 gene (Fsp27) belongs to the cell death-inducing DNA fragmentation factor 45-like effector family. Fsp27 is highly expressed in adipose tissue and fatty liver. In adipocytes, FSP27 localizes to the membrane of lipid droplets and promotes lipid droplet hypertrophy. Recently, FSP27 was shown to consist of two isoforms, FSP27α and FSP27β. Previously, we demonstrated that Fsp27a is directly regulated by peroxisome proliferator-activated receptor γ (PPARγ) in fatty livers of genetically obese leptin deficient ob/ob mice and that Fsp27b may potentially be regulated by different factors transcriptionally as they both have a different promoter region. Thus, the aim of the present study was to elucidate whether Fsp27b is regulated by PPARγ in fatty liver. Fsp27a and Fsp27b were markedly induced in fatty liver of ob/ob mice compared with those in the normal liver. However, both Fsp27a/b were expressed at markedly lower levels in liver-specific PPARγ knockout mice with an ob/ob background. Further, the PPAR response element (PPRE) for the PPARγdependent promotion of Fsp27b promotor activity was revealed at position-1,163/-1,151 from the transcriptional start site (+1). Interestingly, the cis-element responsible for the PPARγ-dependent induction of Fsp27b was the same as that responsible for PPARγ-dependent induction of Fsp27a. These results suggest that PPARγ regulates not only Fsp27a but also Fsp27b in fatty liver of ob/ob mice through a common PPRE.

Roles of PPARα and PPARγ As Regulator of Free Fatty Acids in Nonalcoholic Steatohepatitis

“…Furthermore, the adipocytespecific Fsp27 deletion exacerbates hepatic steatosis after a challenge of high-fat diet. The adipocyte PPARγ-FSP27 cascade may be a key regulator for hepatic fatty homeostasis and suppress the procession of NAFLD/NASH [57][58][59].…”

Transcriptional regulation of adipogenin expression in liver steatosis by hepatic peroxisome proliferator‐activated receptor gamma

“…The reverse primer sequence was common to all constructs: 5 0 -GGCTGCTCCTGAA GACCTGT-3 0 . The PPARγ and RXRα expression vectors were used in our previous studies (Aibara et al, 2018(Aibara et al, , 2020a.…”

“…Fsp27 promotes lipid accumulation in the liver (Matsusue et al, 2008); it has two isoforms: exon1 variants Fsp27α and Fsp27β (Xu et al, 2015). Both isoforms have been found to be PPARγ target genes (Aibara et al, 2020a;Matsusue et al, 2008); these findings indicate that hepatic PPARγ target genes contribute to hepatic lipid accumulation.…”