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