Forskning

July 13, 2020

Caffeine upregulates hepatic sex hormone-binding globulin production by increasing adiponectin through AKT/FOX)1 pathway in white adipose tissue

L Brianso-Llort et al, 2020. Caffeine upregulates hepatic sex hormone-binding globulin production by increasing adiponectin through AKT/FOX)1 pathway in white adipose tissue, Mol Nutr Food Res, published online.

ABSTRACT:

Scope: Epidemiological studies have shown that caffeine increases serum sex hormone-binding globulin (SHBG) levels. The relationship between caffeine and SHBG production has never been studied before at molecular level. The aim of our study was to examine whether caffeine regulates SHBG production and to determine the associated molecular mechanisms.

Methods and results: Two different studies were performed; in vitro studies using human HepG2 cells treated with caffeine (100 μM and 500 μM) and in vivo studies using a humanized SHBG transgenic mice drinking caffeine in the water (0.1 mg/ ml) for 12 days. Our results showed that caffeine did not change SHBG production in HepG2 cells. By contrast, caffeine treatment increased significantly hepatic SHBG production in human SHBG transgenic mice when compared with control mice. Caffeine increased adiponectin levels in epididymal adipose tissue of human SHBG transgenic mice. Moreover, caffeine increased adiponectin production by reducing AKT phosphorylation which increased FOXO1 protein levels in 3T3-L1 mature adipocytes and human SHBG transgenic mice. Finally, caffeine-induced increase in adiponectin in turn upregulated hepatic HNF-4α levels in human SHBG transgenic mice.

Conclusions: Our results showed that caffeine upregulates hepatic SHBG expression by increasing adiponectin production through AKT/FOXO1 pathway in the adipose tissue.