ECE2011 Poster Presentations Obesity (47 abstracts)
TNFα plays an essential role in the downregulation of sex hormone-binding globulin production by decreasing hepatic HNF-4α through NF-κB activation
A Barbosa-Desongles , R Simo , A Lecube , C Hernandez & D Selva
Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca, Barcelona, Spain.
The reason why obesity (a chronic low-grade inflammatory disease) is associated with low levels of sex hormone-binding globulin (SHBG) remains to be elucidated. In the present study we provide evidence that TNFα (a proinflammatory cytokine that increases with obesity) reduces SHBG production by human HepG2 hepatoblastoma cells. The effect of TNFα on human SHBG expression was mediated by NF-κB which causes the downregulation of HNF4α: a key SHBG transcriptional regulator. Moreover, daily TNFα treatment of human SHBG transgenic mice reduced plasma SHBG levels as well as liver HNF4α levels. Finally, a negative and independent correlation was found between plasma levels of TNFα receptor 1 and SHBG in obese patients. We conclude that sustained exposition to elevated levels of TNFα decreases plasma SHBG production by reducing hepatic HNF4α levels via NF-κB activation. These findings open up a new mechanism linking obesity with the deleterious consequences arising from lower levels of SHBG.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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