KMID : 1161520130170050331
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Animal Cells and Systems 2013 Volume.17 No. 5 p.331 ~ p.340
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17¥â-estradiol inhibits PPAR¥á of skeletal muscle
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Lee Hyung-Hee
Yoon Mi-Chung
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Abstract
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To determine whether 17¥â-estradiol regulates peroxisome proliferator-activated receptor ¥á (PPAR¥á)-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 PPAR¥á agonist fenofibrate or 17¥â-estradiol. Both differentiated C2C12 myotubes and skeletal muscle of high-fat diet-fed obese mice showed lipid accumulation. However, either fenofibrate or 17¥â-estradiol decreased lipid droplets and increased mRNA levels of PPAR¥á target enzymes responsible for fatty acid oxidation. When mice and myotubes were concomitantly treated with fenofibrate and 17¥â-estradiol, 17¥â-estradiol reversed the effects of fenofibrate on lipid accumulation and mRNA expression of PPAR¥á target genes. In addition, 17¥â-estradiol not only decreased basal levels of PPAR¥á reporter gene activation but also reduced fenofibrate-induced luciferase reporter activity in C2C12 myoblasts. Moreover, 17¥â-estradiol inhibited the recruitment of the PPAR¥á coactivator CREB-binding protein. These results demonstrate that 17¥â-estradiol inhibits the actions of PPAR¥á on skeletal muscle lipid metabolism by down-regulating the expression of PPAR¥á target genes for fatty acid catabolism, which may be mediated through the inhibition of PPAR¥á-dependent coactivator recruitment.
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KEYWORD
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peroxisome proliferator-activated receptor a, fenofibrate, 17b-estradiol, fatty acid oxidation, skeletal muscle, C2C12 cell, CREB-binding protein
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