[PDF][PDF] mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass

SD Kunkel, M Suneja, SM Ebert, KS Bongers, DK Fox… - Cell metabolism, 2011 - cell.com
SD Kunkel, M Suneja, SM Ebert, KS Bongers, DK Fox, SE Malmberg, F Alipour, RK Shields
Cell metabolism, 2011cell.com
Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacologic
therapy. To develop a potential therapy, we identified 63 mRNAs that were regulated by
fasting in both human and mouse muscle, and 29 mRNAs that were regulated by both
fasting and spinal cord injury in human muscle. We used these two unbiased mRNA
expression signatures of muscle atrophy to query the Connectivity Map, which singled out
ursolic acid as a compound whose signature was opposite to those of atrophy-inducing …
Summary
Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacologic therapy. To develop a potential therapy, we identified 63 mRNAs that were regulated by fasting in both human and mouse muscle, and 29 mRNAs that were regulated by both fasting and spinal cord injury in human muscle. We used these two unbiased mRNA expression signatures of muscle atrophy to query the Connectivity Map, which singled out ursolic acid as a compound whose signature was opposite to those of atrophy-inducing stresses. A natural compound enriched in apples, ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy in mice. It did so by enhancing skeletal muscle insulin/IGF-I signaling and inhibiting atrophy-associated skeletal muscle mRNA expression. Importantly, ursolic acid's effects on muscle were accompanied by reductions in adiposity, fasting blood glucose, and plasma cholesterol and triglycerides. These findings identify a potential therapy for muscle atrophy and perhaps other metabolic diseases.
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