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