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Corticosteroid Binding Globulin: A New Target for Cortisol-Driven Obesity

Laboratoire de Neurogénétique et Stress (O.O., V.G.-D., B.L., P.M., M.-P.M.), Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche 1243-Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 471, Université Victor Segalen Bordeaux 2, Institut François Magendie, 33077 Bordeaux cédex, France; Laboratoire de Génétique Cellulaire (N.I., D.M., C.G., M.Y., J.G.), Centre de Recherche INRA de Toulouse-Auzeville, 31326 Castanet Tolosan cédex France; Station de Génétique Quantitative et Appliquée (J.-P.B.), INRA, 78352 Jouy-en-Josas cédex France; Laboratoire d’Etude et de Recherche sur les Génomes (P.C.), INRA, 78352 Jouy en Josas cédex, France; and INSERM Equipe de Recherche et d’Innovation Méthodologique 322 (A.E.-B., M.P.), Hopital Debrousse, 69322 Lyon cédex 05, France

Address all correspondence and requests for reprints to: Marie-Pierre Moisan, Laboratoire de Neurogénétique et Stress, Institut National de la Santé et de la Recherche Médicale, Unité 471-Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1243, Université Victor Segalen Bordeaux 2, Institut François Magendie, rue Camille Saint Saëns, 33077 Bordeaux cédex, France. E-mail: moisan{at}bordeaux.inserm.fr.

We present data suggesting that corticosteroid-binding globulin (CBG) may be the causal gene of a previously identified quantitative trait locus (QTL) associated with cortisol levels, fat, and muscle content in a pig intercross. Because Cbg in human and mouse maps in the region orthologous to the pig region containing this QTL, we considered Cbg as an interesting positional candidate gene because CBG plays a major role in cortisol bioavailability. Firstly, we cloned pig Cbg from a bacterial artificial chromosome library and showed by fluorescent in situ hybridization and radiation hybrid mapping that it maps on 7q26 at the peak of the QTL interval. Secondly, we detected in a subset of the pig intercross progeny a highly significant genetic linkage between CBG plasma binding capacity values and the chromosome 7 markers flanking the cortisol-associated QTL. In this population, CBG capacity is correlated positively to fat and negatively to muscle content. Thirdly, CBG capacity was three times higher in Meishan compared with Large White parental breeds and a 7-fold difference was found in Cbg mRNA expression between the two breeds. Overall, the data accumulated in this study point to Cbg gene as a key regulator of cortisol levels and obesity susceptibility.

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Ligands:   Hydrocortisone

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