title: mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Kunkel
authors.forename: Manish
authors.initials: M
authors.lastname: Suneja
authors.forename: Scott M
authors.initials: SM
authors.lastname: Ebert
authors.forename: Kale S
authors.initials: KS
authors.lastname: Bongers
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Fox
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Malmberg
authors.forename: Fariborz
authors.initials: F
authors.lastname: Alipour
authors.forename: Richard K
authors.initials: RK
authors.lastname: Shields
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Adams
mesh_terms: D000818:Animals; D002460:Cell Line; D005215:Fasting; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006614:Hindlimb / Q000294:innervation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D014315:Triterpenes; D000097245:Ursolic Acid