Caveolin1 protects against diet induced hepatic lipid accumulation in mice.

Meng Li,Chaohui Yu,Chengfu Xu,Jiewei Wang,Xingyong Wan,Han Ma,Haixiu Huang,Chunxiao Li,Youming Li,Dahua Chen,Jonathan M Peterson

doi:10.1371/journal.pone.0178748

Abstract

Background and aimCaveolin1 (CAV1) is involved in lipid homeostasis and endocytosis, but little is known about the significance of CAV1 in the pathogenesis and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the role of CAV1 in NAFLD.MethodsExpression of CAV1 in the in vitro and in vivo models of NAFLD was analyzed. The effects of CAV1 knockdown or overexpression on free fatty acid (FFA)-induced lipid accumulation in L02 cells and AML12 cells were determined. CAV1 knockout (CAV1-KO) mice and their wild-type (WT) littermates were subjected to a high fat diet (HFD) for 4 weeks, and the functional consequences of losing the CAV1 gene and its subsequent molecular mechanisms were also examined.ResultsNoticeably, CAV1 expression was markedly reduced in NAFLD. CAV1 knockdown led to the aggravation of steatosis that was induced by FFA in both L02 cells and AML12 cells, while CAV1 overexpression markedly attenuated lipid accumulation in the cells. Consistent with CAV1 repression in the livers of HFD-induced mice, the CAV1-KO mice exhibited more severe hepatic steatosis upon HFD intake. In addition, increased cholesterol levels and elevated transaminases were detected in the plasma of CAV1-KO mice. The protein expression of SREBP1, a key gene involved in lipogenesis, was augmented following CAV1 suppression in FFA-treated hepatocytes and in the livers of HFD-fed CAV1-KO mice.ConclusionsCAV1 serves as an important protective factor in the development of NAFLD by modulating lipid metabolism gene expression.

Highlights

Nonalcoholic fatty liver disease (NAFLD), which encompasses a spectrum from simple hepatic steatosis to steatosis combined with varying degrees of inflammation and fibrosis, has become one of the most common liver diseases around the world [1]
CAV1 knockdown led to the aggravation of steatosis that was induced by free fatty acids (FFAs) in both L02 cells and AML12 cells, while CAV1 overexpression markedly attenuated lipid accumulation in the cells
The protein expression of sterol response element binding protein-1 (SREBP1), a key gene involved in lipogenesis, was augmented following CAV1 suppression in FFA-treated hepatocytes and in the livers of high fat diet (HFD)-fed CAV1-KO mice

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD), which encompasses a spectrum from simple hepatic steatosis to steatosis combined with varying degrees of inflammation and fibrosis, has become one of the most common liver diseases around the world [1]. The molecular mechanisms underlying hepatic fat accumulation and the trigger for the subsequent hepatocyte injury remain unclear. The liver plays a central role in whole-body glucose and lipid homeostasis, but studies regarding the role of CAV1 in this organ are still limited. The lack of CAV1 alters hepatocyte energy metabolism homeostasis under physiological and pathological conditions [13]. Despite this recent progress, the precise role of CAV1 in the development of NAFLD remains unclear. Caveolin (CAV1) is involved in lipid homeostasis and endocytosis, but little is known about the significance of CAV1 in the pathogenesis and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the role of CAV1 in NAFLD

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