Sex hormone-binding globulin overexpression protects against high-fat diet-induced obesity in transgenic male mice

Obese subjects of all ages and sex have reduced plasma SHBG levels. Whether these low plasma SHBG levels play a role in obesity development is unknown. In the present work we wanted to explore if SHBG overexpression could prevent obesity development induced by high fat diet (HID). To do so, we fed humanized SHBG transgenic male mice and their wild-type littermates with control diet (CD) or HID over the course of 8 weeks. The results showed that SHBG overexpression protected against body weight gain and fat accumulation induced by HID. In addition, SHBG overexpression also abrogated the increase in insulin, leptin and resistin levels, as well as the reduction in adiponectin, induced by HID. Mechanistically, the SHBG protection against HID-induced obesity was achieved by stimulating lipolysis in white adipose tissue. Furthermore, we have demonstrated the SHBG cell-autonomous effect using human primary visceral adipocytes. Taking together, our results demonstrate that SHBG overexpression protects against diet-induced obesity and improves the metabolic profile of male mice fed a HFD diet. (C) 2020 Elsevier Inc. All rights reserved.