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7 t h E u r o p e a n C o n g r e s s o n
Obesity and
Eating Disorder
Obesity 2018
Journal of Obesity & Eating Disorders
ISSN 2471-8203
A p r i l 1 2 - 1 3 , 2 0 1 8
Am s t e r d a m , N e t h e r l a n d s
Page 38
Low plasma SHBG levels are present in obese subjects of all ages and in
overweight individuals, these are biomarkers for the metabolic syndrome
and predict type 2 diabetes and cardiovascular disease risk. There are no
in vivo models to study SHBG expression and regulation during obesity
development, since rodents unlike humans do not express the SHBG gene
in their livers. In the present study, 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
characterization of this SHBG-C57BL/ksJ-db/db mouse model have allowed
us to determine: (1) the molecular mechanisms and transcription factors
causing the SHBG downregulation during obesity development, which involved
changes in liver HNF-4α and PPARγ mRNA and protein levels. These results
were further confirmed in human liver biopsies; (2) that SHBG overexpression
protects against body weight increase, adiposity and NAFLD development.
The SHBG overexpression in C57BL/ksJ-db/db mice significantly reduced
adipose tissue and liver weight. Overall, we have created the first mouse
model that resembles what occurs in human obese subjects in terms of SHBG
expression and regulation. More importantly, our results point out to SHBG as
a protective factor against adiposity and NAFLD. Therefore, SHBG could be a
new therapeutic target whereby increased expression may reduce obesity and
NAFLD.
Biography
David Martinez Selva received Bachelor’s Degree in Biology in
1996 at the University of Barcelona. He obtained my PhD in Bio-
chemistry and Molecular Biology at the Autonomous University
of Barcelona in 2001. After his PhD he has accepted as a post-
doctoral position for 7 years in Professor Hammond laboratory
first at the LRCC in the UWO, Canada and later on at the Child
and Family Research Institute (CFRI) in the University of British
Columbia (UBC), Vancouver, British Columbia, Canada where he
worked on themolecular mechanisms regulating hepatic SHBG
production in several human SHBG transgenicmice and HepG2
cells. Eight years ago he obtained a principal investigator po-
sition through the Miguel Servet Program in the Diabetes and
MetabolismDepartment at the Vall d’Hebron Research Institute
in Barcelona, Spain.
Sex hormone-binding globulin as a new therapeutic target
against obesity and NAFLD development
David Martinez Selva, Cristina Saez-Lopez, Cristina
Hernandez and Rafael Simo
Vall d’Hebron Research Insitute (VHIR), Spain
David Martinez Selva et al., J Obes Eat Disord 2018, Volume: 4
DOI: 10.21767/2471-8203-C1-008