Potential Role of Tumor Necrosis Factor-α in Downregulating Sex Hormone-Binding Globulin
Simó Canonge, Rafael (Hospital Universitari Vall d'Hebron)
Barbosa-Desongles, Anna
Lecube, Albert
Hernández, Cristina
Martínez Selva, David
Universitat Autònoma de Barcelona

Data:	2012
Resum:	Low plasma sex hormone-binding globulin (SHBG) levels are associated with obesity and predict the development of type 2 diabetes. The reason why obese individuals have low circulating SHBG has been attributed to hyperinsulinemia, but no mechanistic evidence has been described. The aim of the current study is to explore whether tumor necrosis factor-α (TNF-α) rather than insulin could be the main factor accounting for low SHBG levels in obesity. We performed in vitro and in vivo studies using human HepG2 cells and human SHBG transgenic mice. In addition, a cross-sectional study to explore the relationship between TNF-α and SHBG in obese patients and an interventional study to examine the effect of insulin administration on circulating SHBG in type 2 diabetic patients were performed. We provide evidence that TNF-α, but not insulin, is the main factor by which SHBG is reduced in obesity. Plasma SHBG was significantly increased rather than decreased after insulin treatment in diabetic patients. TNF-α-induced reduction of SHBG expression was mediated by downregulating HNF4A. Finally, a negative and independent correlation was found between plasma TNF-α receptor 1 and SHBG levels in obese patients. Our results suggest that TNF-α plays an important role downregulating SHBG in chronic low-grade inflammatory diseases such as obesity and type 2 diabetes.
Nota:	Altres ajuts:D.M.S. received a grant from the Instituto de Salud Carlos III and is the recipient of a Miguel Servet contract. This work is supported by Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM). CIBERDEM is an initiative of Instituto de Salud Carlos III.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Diabetes, Vol. 61 (january 2012) , p. 372-382, ISSN 1939-327X

DOI: 10.2337/db11-0727
PMID: 22210320

11 p, 1.9 MB

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