Corticosteroid binding globulin: A new target for cortisol-driven obesity

Olga Ousova, Véronique Guyonnet-Duperat, Nathalie Iannuccelli, Jean Pierre Bidanel, Denis Milan, Carine Genêt, Bastien Llamas, Martine Yerle, Joël Gellin, Patrick Chardon, Agnès Emptoz-Bonneton, Michel Pugeat, Pierre Mormède, Marie Pierre Moisan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1687-1696
Number of pages10
JournalMolecular Endocrinology
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 2004
Externally publishedYes

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