Enhanced Sarcolemmal FAT/CD36 Content and Triacylglycerol Storage in Cardiac Myocytes From Obese Zucker Rats

Abstract

In obesity, the development of cardiomyopathy is associated with the accumulation of myocardial triacylglycerols (TAGs), possibly stemming from elevation of myocardial long-chain fatty acid (LCFA) uptake. Because LCFA uptake is regulated by insulin and contractions, we examined in cardiac myocytes from lean and obese Zucker rats the effects of insulin and the contraction-mimetic agent oligomycin on the initial rate of LCFA uptake, subcellular distribution of FAT/CD36, and LCFA metabolism. In cardiac myocytes from obese Zucker rats, under basal conditions, FAT/CD36 was relocated to the sarcolemma at the expense of intracellular stores. In addition, the LCFA uptake rate, LCFA esterification rate into TAGs, and the intracellular unesterified LCFA concentration each were significantly increased. All these metabolic processes were normalized by the FAT/CD36 inhibitor sulfo-N-succinimidyloleate, indicating its antidiabetic potential. In cardiac myocytes isolated from lean rats, in vitro administration of insulin induced the translocation of FAT/ CD36 to the sarcolemma and stimulated initial rates of LCFA uptake and TAG esterification. In contrast, in myocytes from obese rats, insulin failed to alter the subcellular localization of FAT/CD36 and the rates of LCFA uptake and TAG esterification. In cardiac myocytes from lean and obese animals, oligomycin stimulated the initial rates of LCFA uptake and oxidation, although oligomycin only induced the translocation of FAT/CD36 to the sarcolemma in lean rats. The present results indicate that in cardiac myocytes from obese Zucker rats, a permanent relocation of FAT/CD36 to the sarcolemma is responsible for myocardial TAG accumulation. Furthermore, in vitro these cardiac myocytes, although sensitive to contraction-like stimulation, were completely insensitive to insulin, as the basal conditions in hyperinsulinemic, obese animals resemble the insulin-stimulated condition in lean littermates.

CD36: Implications in cardiovascular disease

“…In muscle, increased plasma membrane CD36 expression has been shown to occur after muscle contraction and insulin stimulation ,Koonen, et al, 2004,Koonen, Glatz, Bonen, & Luiken, 2005, and analogous to glucose transporter redistribution, may effect energy substrate choice and utilization. In obesity and insulin resistance, there is impairment of this normal recycling, and instead CD36 expression appears locked on the membrane in skeletal muscle ,Coort, et al, 2004. The effect of these conditions on localization of CD36 in other tissues/cells has been less well studied, but one may speculate that changes in CD36 localization (and thus function) in cells which are so intimately involved in glucose and fatty acid metabolism may contribute to insulin resistance states and obesity.…”

Rodent models of diabetic cardiomyopathy

“…Obesity develops because of nonfunctioning leptin receptors, possibly owing to a receptor dimerization defect (Phillips et al, 1996). Zucker fatty rats are hyperphagic, obese and develop increased serum triglyceride, fatty acid and insulin levels, but are not hyperglycemic (Luiken et al, 2001;Coort et al, 2004). The phenotype of the Zucker diabetic fatty rats (ZDF rats) originated from selective breeding of Zucker fatty rats that exhibited high glucose levels, thus ZDF rats are an inbred strain generated from the outbred Zucker fatty rat.…”

Beneficial Effects of Rosuvastatin in Heart of C57Bl/6 Mice with Diet- Induced Metabolic Syndrome - A Preliminary Study

“…This finding showed that the treatment was not effective at reducing lipid capitation by cardiomyocytes, which may be explained by an increase in receptor triglycerides and fatty acids (CD36) in the membranes of cardiomyocytes in obese animals [4,7,35,36].…”