ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP224 | DOI: 10.1530/endoabs.63.GP224

Caffeine upregulates hepatic SHBG production by increasing adiponectin in white adipose tissue

Laura Brianso-Llort, Lidia Fuertes-Rioja, Lorena Ramos Perez, Cristina Hernandez, Rafael Simo & David Selva


Vall d’Hebron Research Institute (VHIR), Barcelona, Spain.


Epidemiological studies have shown that caffeine increases plasma SHBG levels and also reduce the risk of type 2 diabetes. There are no reports describing any molecular mechanism by which caffeine regulates hepatic SHBG production. The aim of the present study was to explore whether caffeine regulates SHBG production and to determine the associated molecular mechanisms. For this purpose, in vitro and in vivo studies were performed using human HepG2 cells and human SHBG transgenic mice. Our results showed that caffeine treatment did not change SHBG production in HepG2 cells. By contrast, caffeine treatment increased significantly both plasma and hepatic mRNA SHBG levels in human SHBG transgenic mice when compared with control mice. Caffeine treatment increased adiponectin mRNA levels in epididymal adipose tissue of human SHBG transgenic mice and in differentiated 3T3-L1 mouse adipocytes. This caffeine-induced increase in adiponectin in turn upregulated the hepatic levels of HNF-4a in human SHBG transgenic mice. Our results showed for the first time that caffeine upregulates hepatic SHBG expression by increasing adiponectin production in the adipose tissue. These results suggest that the beneficial effects of caffeine in preventing type 2 diabetes development could be mediated by increasing SHBG plasma levels.

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