In Vivo Epinephrine-Mediated Regulation of Gene Expression in Human Skeletal Muscle
Nathalie Viguerie,
Karine Clement,
Pierre Barbe,
Melanie Courtine,
Arriel Benis,
Dominique Larrouy,
Blaise Hanczar,
Veronique Pelloux,
Christine Poitou,
Yadh Khalfallah,
Gregory S. Barsh,
Claire Thalamas,
Jean-Daniel Zucker and
Dominique Langin
Unité de Recherches sur les Obésités, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 586 (N.V., P.B., D.Lar., D.Lan.), Institut Louis Bugnard, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, 31403 Toulouse, France; INSERM Avenir and EA3502 Université Paris 6 (K.C., V.P., C.P.), Service de Médecine et Nutrition, Hôtel-Dieu, 75004 Paris, France; Laboratoire d’Informatique Médicale et de Bioinformatique (M.C., A.B., B.H., J.-D.Z.), Faculté de Médecine de Bobigny, Université Paris Nord, 93017 Bobigny, France; INSERM, Unité 449 (Y.K.), Faculté de Médecine R. Laennec, 69372 Lyon, France; Department of Pediatrics and Genetics (G.S.B.), Howard Hugues Medical Institute, Beckman Center, Stanford University School of Medicine, Stanford, California 94305; and Centre d’Investigation Clinique Inserm-Hôpitaux de Toulouse (C.T.), Hôpital Purpan, 31059 Toulouse, France
Address all correspondence and requests for reprints to: Dominique Langin, Unité de Recherche sur les Obésités, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 586, Institut Louis Bugnard, Bâtiment L3, Centre Hospitalier Universitaire Rangueil, 31403 Toulouse Cedex 4, France. E-mail: langin{at}toulouse.inserm.fr.
The stress hormone epinephrine produces major physiologicaleffects on skeletal muscle. Here we determined skeletal musclemRNA expression profiles before and during a 6-h epinephrineinfusion performed in nine young men. Stringent statisticalanalysis of data obtained using 43,000 cDNA element microarraysshowed that 1206 and 474 genes were up- and down-regulated,respectively. Microarray data were validated using reverse transcriptionquantitative PCR. Gene classification was performed throughdata mining of Gene Ontology annotations, cluster analysis ofregulated genes among 14 human tissues, and correlation analysisof mRNA and clinical parameter variations. Evidence of an autoregulatorycontrol was provided by the regulation of key genes of the cAMP-dependenttranscription pathway. Genes with known functional cAMP responseelements were regulated by the hormone. The impact on metabolismwas illustrated by coordinated regulations of genes involvedin carbohydrate and protein metabolisms. Epinephrine had a profoundeffect on genes involved in immunity and inflammatory response,a previously unappreciated aspect of catecholamine action. Informationon 526 mRNAs corresponded to genes of unknown function. Thesedata define the molecular signatures of epinephrine action inhuman skeletal muscle. They may contribute to the understandingof skeletal muscle alterations observed in pathological conditionscharacterized by sympathetic nervous system overdrive.
This work was supported by grants from INSERM (CIC-Merck ClinicalResearch Program) (to D.Lan. and P.B.), Action ThématiqueConcertée INSERM en Nutrition (to D.Lan. and K.C.), andFondation Claude Bernard (to K.C.).
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