ECE2014 Poster Presentations Obesity (53 abstracts)
Adiponectin upregulates SHBG production: molecular mechanisms and potential implications
Rafael Simo 1 , Cristina Saez Lopez 1 , Albert Lecube 2 , Cristina Hernandez 1 , Jose Manuel Fort 3 & David M Selva 1
1Vall Hebron Research Institute (VHIR), Barcelona, Spain; 2Hospital Arnau de Vilanova, Lleida, Spain; 3Hospital Universitari Vall Hebron, Barcelona, Spain.
Epidemiological studies have shown that plasma SHBG levels correlate with plasma adiponectin levels, both in men and women. To the best of our knowledge there are no reports describing any molecular mechanism by which adiponectin regulates hepatic SHBG production. The aim of the present study is to explore whether adiponectin regulates SHBG production by increasing HNF-4α levels through reducing hepatic lipid content. For this purpose, in vitro studies using human HepG2 cells, as well as human liver biopsies were performed. Adiponectin treatment increased SHBG production via AMPK activation in HepG2 cells. Adiponectin treatment decreased the mRNA and protein levels of enzymes related to hepatic lipogenesis (ACC) and increased those related to fatty acid oxidation (ACOX and CPTI). These adiponectin-induced changes in hepatic enzymes resulted in a reduction of total TG and FFA and an increase of HNF-4α. When HNF-4α expression was silenced by using siRNA, adiponectin-induced SHBG overexpression was blocked. Furthermore, adiponectin-induced upregulation of SHBG production via HNF-4α overexpression was abrogated by the inhibition of fatty acid oxidation or by the induction of lipogenesis with a 30 mM glucose treatment in HepG2 cells. Finally, adiponectin levels correlated positively and significantly with both HNF-4α and SHBG mRNA levels in human liver biopsies. Our results suggest that adiponectin increases SHBG production by activating AMPK which reduces hepatic lipid content and increases HNF-4α levels.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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