Sexual dimorphism in body fat regulation

描述（由申请人提供）：肥胖及其相关合并症的患病率正迅速达到流行病的程度。雄性和雌性保持着不同的脂肪分布模式。男性倾向于积累更多的内脏脂肪，而女性则有更多的皮下脂肪。维持典型脂肪分布的现象表明了身体脂肪调节的性别特异性机制。当雌性在热量限制或脂肪去除后减少能量消耗以保存能量时，雄性表现出嗜食以恢复脂肪。我们的实验室发现，缺乏syndecan-3的小鼠抵抗饮食引起的肥胖，并表现出更好的葡萄糖耐量，这是由于雄性的热量摄入减少，而雌性的能量消耗增加。靶向破坏编码粒细胞巨噬细胞集落刺激因子的基因的小鼠会增加脂肪。雄性的热量摄入增加，而雌性的能量消耗减少。这些数据表明，雄性和雌性使用不同的策略来调节能量平衡。这一提议的总体目标是测试关于男性和女性之间的机制差异的具体假设，这些机制差异导致了不同的身体脂肪积累和不同的身体脂肪防御策略。

DESCRIPTION (provided by applicant): The prevalence of obesity with its associated co-morbidities is rapidly reaching epidemic proportions. Males and females maintain distinctive fat distribution patterns. Males tend to accumulate more visceral fat whereas females have more subcutaneous fat. The phenomenon of maintaining typical fat distributions suggests sex-specific mechanisms of body fat regulation. While females decrease energy expenditure to conserve energy during caloric restriction or after fat removal, males exhibit hyperphagia to restore fat. Our lab has found that syndecan-3-deficient mice resist diet-induced obesity and show improved glucose tolerance, the result of decreased caloric intake in males whereas increased energy expenditure in females. Mice with targeted disruption of the gene encoding granulocyte macrophage-colony stimulating factor gain fat. Males show increased caloric intake while females show reduced energy expenditure. These data suggest that males and females use distinct strategies to regulate energy balance. The overall goal for this proposal is to test specific hypotheses about the mechanistic differences between males and females that result in different body-fat accumulation and different strategies by which that body fat is defended.