β2GPI exerts an anti-obesity effect in female mice by inhibiting lipogenesis and promoting lipolysis

In humans, males compared to females have increased visceral adipose tissue which contributes to their increased risk of early death. Mice display analogous sexual diamorphism whereby females are protected from weight gain when fed a high fat diet compared to males. A role has recently been reported for beta(2)-glycoprotein I, an abundant plasma protein, in healthy leanness in humans. In this study we investigated the role of beta(2)-glycoprotein I in fat metabolism in male and female mice fed a normal chow or high fat diet. We have made a number of novel insights into factors contributing to sexual diamorphism in obesity. Female wild type mice are protected from obesity when fed a high fat diet due to down regulation of lipogenesis in the visceral adipose tissues. This down regulation is due to beta(2)-glycoprotein I as female mice deficient in this protein have increased levels of lipogenesis enzymes in their visceral adipose tissues with an accompanying increase in weight compared to female wild type controls. Understanding female specific regulators of obesity may lead to sex specific anti-obesity therapies to address this major health problem.