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 (HFD). To do so, we fed humanized SHBG transgenic male mice and their wild-type littermates with control diet (CD) or HFD over the course of 8 weeks. The results showed that SHBG overexpression protected against body weight gain and fat accumulation induced by HFD. In addition, SHBG overexpression also abrogated the increase in insulin, leptin and resistin levels, as well as the reduction in adiponectin, induced by HFD. Mechanistically, the SHBG protection against HFD-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.

所有年龄和性别的肥胖受试者的血浆SHBG水平降低。这些低血浆SHBG水平是否在肥胖症发展中起作用尚不清楚。在目前的工作中，我们想探讨SHBG的过度表达是否可以预防由高脂饮食（HFD）引起的肥胖症发展。为此，我们喂饱了人性化的SHBG转基因雄性小鼠及其野生型同窝仔在8周的过程中具有对照饮食（CD）或HFD。结果表明，SHBG的过量表达可防止HFD引起的体重增加和脂肪堆积。此外，SHBG的过表达也消除了由HFD引起的胰岛素，瘦素和抵抗素水平的增加以及脂联素的减少。从机理上讲，通过刺激白色脂肪组织中的脂解作用来实现SHBG对HFD诱导的肥胖的保护作用。此外，我们已经证明了使用人原发性内脏脂肪细胞的SHBG细胞自主作用。综上所述，我们的结果表明，SHBG过表达可以防止饮食引起的肥胖，并改善饲喂HFD饮食的雄性小鼠的代谢状况。