Corticosteroid binding globulin: a new target for cortisol-driven obesity.
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.
Ousova
Olga
O
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.
Guyonnet-Duperat
Véronique
V
Iannuccelli
Nathalie
N
Bidanel
Jean-Pierre
JP
Milan
Denis
D
Genêt
Carine
C
Llamas
Bastien
B
Yerle
Martine
M
Gellin
Joël
J
Chardon
Patrick
P
Emptoz-Bonneton
Agnès
A
Pugeat
Michel
M
Mormède
Pierre
P
Moisan
Marie-Pierre
MP
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*
D012333:RNA, Messenger; D014156:Transcortin; D006854:Hydrocortisone