Figure 4: Effects of CD36 in pathological and physiological cardiac hypertrophy.
Under pressure overload, intranuclear PPARa and PGC1a are downregulated and lead to decreased CD36 expression and LCFA uptake by myocardial cells, resulting in an insufficient energy state. At the same time, the activity of HSL and DAGL that break down fat decreases, while fat synthesis-related enzymes, including SREBP-1c, SCD1, SCD2 and GPAT et al., are not down-regulated, leading to the accumulation of toxic lipids. Accumulated lipids and insufficient energy support both contribute to the development of pathological cardiac hypertrophy. During regular exercise, intranuclear PPARa and PGC1a increase and upregulate CD36 and fatty acid transfer rate-limiting enzyme CPT1, thus facilitating the uptake and utilization of LCFA. With the increase of CPT1 on mitochondrial outer membrane, more LCFA undergo aerobic oxidation in mitochondria. The increase of PPARa and PGC1a would also promote the transcription of mitochondrial oxidative phosphorylation-related proteins, which jointly improves the efficiency of fatty acid oxidation. Moreover, fat synthesis-related enzymes, including SREBP -1c, SCD1, SCD2 and GPAT et al and the activity of HSL and DAGL that break down fat are both up-regulated, thereby avoiding excessive accumulation of toxic lipids. Sufficient energy and less toxic lipids maintain the proper cardiac function of physiological cardiac hypertrophy. SREBP-1c, sterol-responsive element-binding protein-1c; SCD1, stearoyl-CoA desaturase 1; SCD2, stearoyl-CoA desaturase 2; GPAT, Glycerol-3-phosphate acyltransferase; HSL, hormone-sensitive lipase; DAGL, diacylglycerol lipase