17b-estradiol inhibits PPAR(a) of skeletal muscle
2013
Lee, H.H., Mokwon University, Daejeon, Republic of Korea | Yoon, M.C., Mokwon University, Daejeon, Republic of Korea
To determine whether 17b-estradiol regulates peroxisome proliferator-activated receptor a(PPARa)-mediated lipid reduction in skeletal muscle cells and tissues and to investigate the molecular mechanism involved in this process, C2C12 myotubes and female ovariectomized C57BL/6J mice were treated with combinations of the PPARa agonist fenofibrate or 17b-estradiol. Both differentiated C2C12 myotubes and skeletal muscle of high-fat diet-fed obese mice showed lipid accumulation. However, either fenofibrate or 17b-estradiol decreased lipid droplets and increased mRNA levels of PPARa target enzymes responsible for fatty acid oxidation. When mice and myotubes were concomitantly treated with fenofibrate and 17b-estradiol, 17b-estradiol reversed the effects of fenofibrate on lipid accumulation and mRNA expression of PPARa target genes. In addition, 17b-estradiol not only decreased basal levels of PPARa reporter gene activation but also reduced fenofibrate-induced luciferase reporter activity in C2C12 myoblasts. Moreover,17b-estradiol inhibited the recruitment of the PPARa coactivator CREB-binding protein. These results demonstrate that 17b-estradiol inhibits the actions of PPARa on skeletal muscle lipid metabolism by down-regulating the expression of PPARa target genes for fatty acid catabolism, which may be mediated through the inhibition of PPARa-dependent coactivator recruitment.
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