Biological Mechanisms and Related Natural Inhibitors of CD36 in Nonalcoholic Fatty Liver

Abstract

Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disorders from non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), is the leading etiology of chronic liver disease and its global prevalence is increasing. Hepatic steatosis, a condition marked by an abnormal buildup of triglycerides in the liver, is the precursor to NAFLD. Differentiated cluster 36 (CD36), a scavenger receptor class B protein, is a membrane receptor that recognizes multiple lipid and nonlipid ligands. It is generally agreed that CD36 contributes significantly to hepatic steatosis by taking part in fatty acid uptake as well as triglyceride storage and secretion. While there has not been any conclusive research on how CD36 inhibitors prevent NAFLD from progressing and no clinically approved CD36 inhibitors are currently available for use in NAFLD, CD36 remains a target worthy of further investigation in NAFLD. In recent years, the potential role of natural products acting through CD36 in treating non-alcoholic fatty liver disease has attracted much attention. This paper offers an overview of the pathogenesis of CD36 in NAFLD and summarizes some of the natural compounds or extracts that are currently being investigated for modulating NAFLD via CD36 or the CD36 pathway, providing an alternative approach to the development of CD36-related drugs in NAFLD.

Integration of transcriptomics and metabonomics revealed the protective effects of hemp seed oil against methionine–choline-deficient diet-induced non-alcoholic steatohepatitis in mice

“…It is generally agreed that CD36 contributes significantly to hepatic steatosis by taking part in fatty acid uptake as well as triglyceride storage and secretion. 33 PPARα, which can promote hepatic fatty acid β-oxidation, plays a significant role as a lipid sensor in the regulation of systemic lipid metabolism and energy homeostasis. 34 Administration of hemp seed oil resulted in reversed expression of these genes in NASH mice, suggesting the involvement of the corresponding pathways in the protective effects of hemp seed oil against MCD diet-induced NASH in mice.…”

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

“…Hepatocytes subsequently increase fatty acid uptake in response, which is mainly mediated by lipid transporters such as Cluster Determinant 36 (CD36) and Fatty Acid Transporter Proteins (FATPs) (Figure 1). CD36 is mainly located at the plasma membrane and plays important roles in hepatic lipid transport, oxidation, and synthesis, which are regulated by various upstream factors such as Peroxisome Proliferator-Activated Receptor γ (PPARγ) and Arylhydrocarbon Receptor (AhR) [15,16]. After palmitoylation, CD36 is able to recognize and capture fatty acids, followed by depalmitoylation to initiate endocytosis to transport fatty acids into cells [17].…”

Druggable targets for the immunopathy of Alzheimer's disease

“…112 The development of SR inhibitors is evolving for indications other than AD, with atherosclerosis, liver disease and cancer at the forefront. 113 To identify a natural product starting point for compound discovery, Wang et al performed an ELISA-like highthroughput screening assay of microbial secondary metabolite crude extracts to identify rosmarinic acid and salvianolic acid B as CD36 SR antagonists. 114 Various molecular modelling studies of SRs have aided the subsequent design of synthetic antagonists including novel sulfatides and indolinylthiazoles.…”