CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting

Abstract

The cluster of differentiation 36 (CD36) is a scavenger receptor present on various types of cells and has multiple biological functions that may be important in inflammation and in the pathogenesis of metabolic diseases, including diabetes. Here, we consider recent insights into how the CD36 response becomes deregulated under metabolic conditions, as well as the therapeutic benefits of CD36 inhibition, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with metabolic diseases. To facilitate this process further, it is important to pinpoint regulatory mechanisms that are relevant under physiological and pathological conditions. In particular, understanding the mechanisms involved in dictating specific CD36 downstream cellular outcomes will aid in the discovery of potent compounds that target specific CD36 downstream signaling cascades.

Lipotoxicity in a Vicious Cycle of Pancreatic Beta Cell Exhaustion

“…TAGs are split to Lc-FFAs by lipases of the digestive juices releasing, among others, palmitate (C16:0, saturated), oleate (C18:1, mono-unsaturated), and linoleate (C18:2, poly-unsaturated) [ 20 ]. Beta cell exposure to Lc-FFAs activates CD36 FFA receptors in the cell membrane which play an important role in the uptake of FFAs and have multiple biological functions that may be important in inflammation and in the development of metabolic diseases, including diabetes [ 19 ]. The upregulation of the CD36 transporter in beta-cells increases the uptake of FFAs, resulting in enhanced GSIS and impaired oxidative metabolism [ 63 , 64 , 65 ].…”

“…Beta cells express the FFA transporter cluster of differentiation 36 (CD36), also known as fatty acid translocase (FAT) [ 19 ], and FFA receptors (FFAR1, FFAR2, and FFAR3). Short-chain FFAs (Sc-FFAs), produced by gut microbiota, target FFAR2 and FFAR3, but their role in beta cell function is unclear [ 20 ].…”

An Overview of Glycosylation and its Impact on Cardiovascular Health and Disease

“…These results coincide with increases of FAT/CD36, higher LCFA uptake, and impaired insulin signaling, which reduced GLUT4 translocation, as observed in DM2 ( Coort et al, 2007 ). The therapeutic potential of CD36 has been suggested although more studies are needed to fully understand signal transduction ( Karunakaran et al, 2021 ). In this sense, the HBP and O -GlcNAcylation possibly represent a novel regulator of cardiac metabolism because acute modulation by the HBP and O -GlcNAc of heart proteins stimulate fatty acid oxidation, probably by increasing FAT/CD36 in the plasma membrane ( Laczy et al, 2011 ).…”

Selenoprotein K contributes to CD36 subcellular trafficking in hepatocytes by accelerating nascent COPII vesicle formation and aggravates hepatic steatosis

“…CD36 is a widely expressed transmembrane glycoprotein which serves many functions in lipid metabolism and signaling [ [5] , [6] , [7] , [8] ]. Anomalously elevated CD36 increases fatty acid (FA) uptake and lipid accumulation in liver cells, drives hepatosteatosis onset and oxidative stress, indisputably contributes to the progression of NAFLD in rodents and patients [ 9 ].…”