The regulation of TFEB in lipid homeostasis of non-alcoholic fatty liver disease: Molecular mechanism and promising therapeutic targets

Life Sci. 2020 Apr 1:246:117418. doi: 10.1016/j.lfs.2020.117418. Epub 2020 Feb 10.

Authors

Shenglan Yu¹, Zhengtao Wang², Lili Ding³, Li Yang⁴

Affiliations

¹ Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
² Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China.
³ Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China. Electronic address: liliding@shutcm.edu.cn.
⁴ Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: yl7@shutcm.edu.cn.

PMID: 32057899
DOI: 10.1016/j.lfs.2020.117418

Abstract

Nonalcoholic fatty liver disease (NAFLD), which is characterized by disruption of lipid homeostasis, has been the leading cause of chronic liver disease worldwide. However, currently there is no effective therapy for NAFLD. Consequently, it is extremely urgent to explore the specific and effective target functioned as lipids regulator during the pathological process of NAFLD for the drug development. Transcription factor EB (TFEB) plays a crucial role in the regulation of lipid homeostasis through linking autophagy to energy metabolism at the transcriptional level. In this review, we summarize the currently available information regarding the mediation of TFEB in lipid metabolism during the pathological process of NAFLD, and the specific regulatory mechanism of TFEB activity. We further recapitulate TFEB as a promising therapeutic target for NAFLD, primarily through the regulation of lipid homeostasis, energy metabolism as well as immune defense. A better understanding of these key issues will be helpful to promote the development of therapeutic agents which specifically target TFEB to halt or reverse the pathological progression of NAFLD.

Keywords: Autophagy; Lipid metabolism; Lysosome function; NAFLD; Transcription factor EB.

Publication types

Review

MeSH terms

Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / antagonists & inhibitors*
Humans
Lipid Metabolism* / drug effects
Non-alcoholic Fatty Liver Disease / drug therapy*
Non-alcoholic Fatty Liver Disease / metabolism

Substances

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
TFEB protein, human