Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 EP602 | DOI: 10.1530/endoabs.37.EP602

ECE2015 Eposter Presentations Obesity and cardiovascular endocrinology (108 abstracts)

SHBG-C57BL/ksJ-db/db: a new mouse model to study the link between SHBG regulation and obesity development

Cristina Sáez López , Cristina Hernández , Rafael Simó & David Martínez Selva


Vall d’Hebron Research Institute, Barcelona, Spain.


Low plasma SHBG levels in overweight individuals are a biomarker for the metabolic syndrome and are predictive of type 2 diabetes and risk of cardiovascular disease. There are no in vivo models to study SHBG expression and regulation during obesity development. The main reason for this is that the obesity-prone rodent models cannot be used to study this issue since rodents unlike humans do not express the SHBG gene in their livers. We have developed by crossing the human SHBG transgenic mice with the C57BL/ksJ-db/db mice, a unique mouse model that expresses the human SHBG and it develops obesity. We have also used a set of human liver biopsies. The results obtained with the SHBG-C57BL/ksJ-db/db mouse model have allowed us to determine that the SHBG overexpression in the C57BL/ksJ-db/db reduced the body weight gain but did not change the metabolic profile of these mice. Moreover, we elucidated the molecular mechanisms and transcription factors causing the SHBG downregulation during obesity development, which involved changes in liver hepatocyte nuclear factor 4 alpha (HNF4α) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and protein levels. Furthermore, these results were confirmed using human liver biopsies. Finally, obese mice had reduced plasma SHBG and total and free testosterone levels when compared to lean mice. We have created the first mouse model that resembles what occurs in human obese subjects in terms of SHBG expression and regulation as well as the reduction of total and free testosterone levels. Future research using this unique mouse model will determine the role of SHBG in the development and progression of obesity, type 2 diabetes or fatty liver disease.

Disclosure: This work was supported by two grants from the Instituto de Salud Carlos III: CP08/00058, PI09/144, PI12/01357 and CIBERDEM (CIBER de Diabetes y Enfermedades Metabólicas Asociadas) an initiative of Instituto de Salud Carlos III.

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