title: SHBG-C57BL/ksJ-db/db: A New Mouse Model to Study SHBG Expression and Regulation During Obesity Development.
abstract: Low plasma sex hormone-binding globulin (SHBG) levels in overweight individuals are a biomarker for the metabolic syndrome and are predictive of type 2 diabetes and cardiovascular disease risk. 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, because rodents, unlike humans, do not express the SHBG gene in their livers. We have developed a unique mouse model that expresses the human SHBG, and it develops obesity, by crossing the human SHBG transgenic mice with the C57BL/ksJ-db/db mice. 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 down-regulation during obesity development, which involved changes in liver hepatocyte nuclear factor 4α and peroxisome proliferator-activated receptor-γ mRNA and protein levels. Furthermore, these results were confirmed using human liver biopsies. Importantly, we also showed that this model resembles what occurs in human obese subjects, because plasma SHBG and total testosterone levels where reduced in obese mice when compared with lean mice. 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.
authors.affiliation: Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca, Universitat Autònoma de Barcelona and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (Instituto Carlos III), 08035 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Saéz-López
authors.affiliation: Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca, Universitat Autònoma de Barcelona and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (Instituto Carlos III), 08035 Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Rivera-Giménez
authors.affiliation: Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca, Universitat Autònoma de Barcelona and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (Instituto Carlos III), 08035 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández
authors.affiliation: Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca, Universitat Autònoma de Barcelona and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (Instituto Carlos III), 08035 Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
authors.affiliation: Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca, Universitat Autònoma de Barcelona and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (Instituto Carlos III), 08035 Barcelona, Spain.
authors.forename: David M
authors.initials: DM
authors.lastname: Selva
mesh_terms: D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012738:Sex Hormone-Binding Globulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D051557:Hepatocyte Nuclear Factor 4; C496593:Hnf4a protein, mouse; D047495:PPAR gamma; D012738:Sex Hormone-Binding Globulin