Sexual dimorphism in body fat regulation

描述(由申请人提供)：肥胖症及其相关共病的流行率正在迅速达到流行病的程度。雄性和雌性都保持着独特的脂肪分布模式。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，身体脂肪调节的机制具有性别特异性。当女性在卡路里限制或脂肪去除后减少能量消耗以保存能量时，男性表现出吞噬功能以恢复脂肪。我们的实验室发现，Syndecan-3缺陷小鼠抵抗饮食诱导的肥胖，并表现出改善的葡萄糖耐量，这是雄性减少卡路里摄入量而雌性增加能量消耗的结果。编码粒细胞-巨噬细胞集落刺激因子的基因被定向破坏的小鼠会增加脂肪。男性的卡路里摄入量增加，而女性的能量消耗减少。这些数据表明，男性和女性使用不同的策略来调节能量平衡。这项提议的总体目标是测试关于男性和女性之间的机械差异导致不同的体脂积累和保护体脂的不同策略的具体假设。

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.