Adipose tissue dysfunction is closely associated with the development and progression of
nonalcoholic fatty liver disease (
NAFLD). Recent studies have implied an important role of prohibitin-1 (PHB1) in adipose tissue function. In the current study, we aimed to explore the function of adipocyte PHB1 in the development and progression of
NAFLD. The PHB1
protein levels in adipose tissues were markedly decreased in mice fed a high-fat diet (HFD) compared to those fed a chow diet. To explore the function of adipocyte PHB1 in the progression of
NAFLD, mice with adipocyte-specific (adipo) deletion of Phb1 (Phb1adipo-/- mice) were generated. Notably, Phb1adipo-/- mice did not develop
obesity but displayed severe
liver steatosis under HFD feeding. Compared to HFD-fed wild-type (WT) mice, HFD-fed Phb1adipo-/- mice displayed dramatically lower fat mass with significantly decreased levels of total adipose tissue
inflammation, including macrophage and neutrophil number as well as the expression of inflammatory mediators. To our surprise, although
liver steatosis in Phb1adipo-/- mice was much more severe, liver
inflammation and
fibrosis were similar to WT mice after HFD feeding.
RNA sequencing analyses revealed that the
interferon pathway was markedly suppressed while the
bone morphogenetic protein 2 pathway was significantly up-regulated in the liver of HFD-fed Phb1adipo-/- mice compared with HFD-fed WT mice. Conclusion: HFD-fed Phb1adipo-/- mice display a subtype of the lean
NAFLD phenotype with severe hepatic steatosis despite low adipose mass. This subtype of the lean
NAFLD phenotype has similar
inflammation and
fibrosis as obese
NAFLD in HFD-fed WT mice; this is partially due to reduced total adipose tissue
inflammation and the hepatic
interferon pathway.