SREBP Regulation of Lipid Metabolism in Liver Disease, and Therapeutic Strategies

Author:

Li Na12ORCID,Li Xiaodan12,Ding Yifu3,Liu Xiao4,Diggle Karin4,Kisseleva Tatiana4,Brenner David A.45

Affiliation:

1. College of Medical Technology, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China

2. Graduate School of Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

3. State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Shanghai 200031, China

4. Department of Surgery, University of California San Diego, La Jolla, CA 92093, USA

5. Sanford Burnham Prebys, La Jolla, CA 92037, USA

Abstract

Sterol regulatory element-binding proteins (SREBPs) are master transcription factors that play a crucial role in regulating genes involved in the biogenesis of cholesterol, fatty acids, and triglycerides. As such, they are implicated in several serious liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). SREBPs are subject to regulation by multiple cofactors and critical signaling pathways, making them an important target for therapeutic interventions. In this review, we first introduce the structure and activation of SREBPs, before focusing on their function in liver disease. We examine the mechanisms by which SREBPs regulate lipogenesis, explore how alterations in these processes are associated with liver disease, and evaluate potential therapeutic strategies using small molecules, natural products, or herb extracts that target these pathways. Through this analysis, we provide new insights into the versatility and multitargets of SREBPs as factors in the modulation of different physiological stages of liver disease, highlighting their potential targets for therapeutic treatment.

Funder

National Natural Science Foundation of China

Shanghai Pujiang Program

National Institutes of Health USA

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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