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Tissue-specific decline in the orphan nuclear estrogen-related receptor alpha and its target medium-chain acyl-CoA dehydrogenase levels in aged female mice

Harmit S.Ranhotra

The estrogen-related receptor alpha (ERR) is a gene regulator that modulates target genes controlling metabolic and various functions and actively promotes energy homeostasis in animals. Since aging in animals is characterized by deregulation in energy homeostasis, whether ERR level undergoes modulation during aging was investigated. Western analysis demonstrated positive ERR expression in various tissues, with the heart expressing the highest ERR level. The level of ERR in old (24 months) mice’s heart, kidney and skeletal muscle was significantly reduced (by 46.50%, 38.40% and 30.30%, respectively) compared to young (3 months) mice. Moreover, ERR level was unchanged in the small intestine, liver, lung, uterus and brain of old mice as compared to young animal. The level of ERR-inducible enzyme,medium-chain acyl-CoAdehydrogenase (MCAD) was also reduced in the heart (by 35%), kidney (by 40%) and skeletalmuscle (by 25%), including liver (by 30%) in old mice, but not in other tissues. The unchanged ERR level in these tissuesmay be beneficial and help maintain tissue energy balance and other functions. However, decreased cardiac, renal and muscle ERR along with MCAD level in the old animal might disturb normal nutrient-sensing pathways which may have a negative effect on energy generation and homeostasis.