CD36 actions in the heart: Lipids, calcium, inflammation, repair and more?

Abstract

CD36 is a multifunctional immuno-metabolic receptor with many ligands. One of its physiological functions in the heart is the high-affinity uptake of long-chain fatty acids (FAs) from albumin and triglyceride rich lipoproteins. CD36 deletion markedly reduces myocardial FA uptake in rodents and humans. The protein is expressed on endothelial cells and cardiomyocytes and at both sites is likely to contribute to FA uptake by the myocardium. CD36 also transduces intracellular signaling events that influence how the FA is utilized and mediate metabolic effects of FA in the heart. CD36 mediated signaling regulates AMPK activation in a way that adjusts oxidation to FA uptake. It also impacts remodeling of myocardial phospholipids and eicosanoid production, effects exerted via influencing intracellular calcium (iCa2+) and the activation of phospholipases. Under excessive FA supply CD36 contributes to lipid accumulation, inflammation and dysfunction. However, it is also important for myocardial repair after injury via its contribution to immune cell clearance of apoptotic cells. This review describes recent progress regarding the multiple actions of CD36 in the heart and highlights those areas requiring future investigation.

Upregulation of free fatty acid receptors in periodontal tissues of patients with metabolic syndrome and periodontitis

“…The role of GPR40 and CD36 in the upregulation of proinflammatory cytokine expression was further supported by our findings that inhibition of GPR40 or CD36 attenuated proinflammatory cytokine expression in gingival fibroblasts stimulated by palmitate and LPS (Figure ). Consistently, studies from other laboratories have also demonstrated a vital role of free fatty acid receptors GPR40 and CD36 in SFA‐promoted inflammation …”

“…Consistently, studies from other laboratories have also demonstrated a vital role of free fatty acid receptors GPR40 and CD36 in SFA-promoted inflammation. 31,32 Regulation of surface receptor expression is a well-known cell function to control cellular response to ligands or uptake of ligands. 33,34 Under certain conditions, cells either upregulate or downregulate the receptor expression, resulting in increased or decreased cell response to ligands and ligand uptake, respectively.…”

Gene expression and morphological changes in the intestinal mucosa associated with increased permeability induced by short‐term fasting in chickens

“…Prolonged fasting has recently been suggested to be involved in intestinal inflammation because of reduced serum antioxidant levels (Abdeen, Mathew, Khan, Dashti, & Asfar, ) and increased immunoglobulin (Lara‐Padilla et al., ) in humans. Cluster differentiation (CD‐36) has been involved in fatty acid transportation (Kitessa et al., ), although recently it has been associated with binding with a pro‐inflammatory cytokine, TLR‐4 (toll‐like receptor‐4) (Abumrad & Goldberg, ). Toll‐like receptors ‐4 binds with the bacterial toxins and has been involved in gut inflammation (Andrade et al., ).…”

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

“…The TGs in CM particles are hydrolyzed by LPL in adipose, skeletal muscle, and heart vascular beds to deliver FFAs for cellular uptake facilitated by membrane cluster of differentiation 36 (CD36) (3). These tissues quantitatively contribute to CM clearance in humans (4)(5)(6) and express high levels of CD36 at the level of both endothelial and parenchymal cells (7,8). Elevated concentrations of postprandial CM remnants after an oral fat load were reported in four subjects with complete CD36 deficiency (9), suggesting that low CD36 might impair CM clearance and result in sustained high levels of circulating CM remnants (10,11).…”