title: Corticosteroid binding globulin: a new target for cortisol-driven obesity.
abstract: 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.
authors.affiliation: Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1243-Institut National de la Santé et de la Recherche Médicale Unité 471, Université Victor Segalen Bordeaux 2, Institut François Magendie, 33077 Bordeaux, France.
authors.forename: Olga
authors.initials: O
authors.lastname: Ousova
authors.forename: Véronique
authors.initials: V
authors.lastname: Guyonnet-Duperat
authors.forename: Nathalie
authors.initials: N
authors.lastname: Iannuccelli
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bidanel
authors.forename: Denis
authors.initials: D
authors.lastname: Milan
authors.forename: Carine
authors.initials: C
authors.lastname: Genêt
authors.forename: Bastien
authors.initials: B
authors.lastname: Llamas
authors.forename: Martine
authors.initials: M
authors.lastname: Yerle
authors.forename: Joël
authors.initials: J
authors.lastname: Gellin
authors.forename: Patrick
authors.initials: P
authors.lastname: Chardon
authors.forename: Agnès
authors.initials: A
authors.lastname: Emptoz-Bonneton
authors.forename: Michel
authors.initials: M
authors.lastname: Pugeat
authors.forename: Pierre
authors.initials: P
authors.lastname: Mormède
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Moisan
mesh_terms: D002001:Adipose Tissue, Brown / Q000502:physiology; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D020022:Genetic Predisposition to Disease; D006854:Hydrocortisone / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D040641:Quantitative Trait Loci; D012333:RNA, Messenger; D017421:Sequence Analysis; D013045:Species Specificity; D034421:Sus scrofa / Q000235:genetics*; D014156:Transcortin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D014156:Transcortin; D006854:Hydrocortisone