GSBS Student Publications

Title

The Lipid Droplet Protein Hypoxia-inducible Gene 2 Promotes Hepatic Triglyceride Deposition by Inhibiting Lipolysis

Student Author(s)

Laura V. Danai

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Program in Molecular Medicine

Date

6-12-2015

Document Type

Article

Disciplines

Biochemistry | Cellular and Molecular Physiology | Lipids

Abstract

The liver is a major site of glucose, fatty acid, and triglyceride (TG) synthesis and serves as a major regulator of whole body nutrient homeostasis. Chronic exposure of humans or rodents to high-calorie diets promotes non-alcoholic fatty liver disease, characterized by neutral lipid accumulation in lipid droplets (LD) of hepatocytes. Here we show that the LD protein hypoxia-inducible gene 2 (Hig2/Hilpda) functions to enhance lipid accumulation in hepatocytes by attenuating TG hydrolysis. Hig2 expression increased in livers of mice on a high-fat diet and during fasting, two states associated with enhanced hepatic TG content. Hig2 expressed in primary mouse hepatocytes localized to LDs and promoted LD TG deposition in the presence of oleate. Conversely, tamoxifen-inducible Hig2 deletion reduced both TG content and LD size in primary hepatocytes from mice harboring floxed alleles of Hig2 and a cre/ERT2 transgene controlled by the ubiquitin C promoter. Hepatic TG was also decreased by liver-specific deletion of Hig2 in mice with floxed Hig2 expressing cre controlled by the albumin promoter. Importantly, we demonstrate that Hig2-deficient hepatocytes exhibit increased TG lipolysis, TG turnover, and fatty acid oxidation as compared with controls. Interestingly, mice with liver-specific Hig2 deletion also display improved glucose tolerance. Taken together, these data indicate that Hig2 plays a major role in promoting lipid sequestration within LDs in mouse hepatocytes through a mechanism that impairs TG degradation.

Rights and Permissions

Citation: J Biol Chem. 2015 Jun 12;290(24):15175-84. doi: 10.1074/jbc.M115.650184. Epub 2015 Apr 28. Link to article on publisher's site

DOI of Published Version

10.1074/jbc.M115.650184

Related Resources

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

25922078