Jeffery Elise, Wing Allison, Holtrup Brandon, Sebo Zachary, Kaplan Jennifer L, Saavedra-Peña Rocio, Church Christopher D, Colman Laura, Berry Ryan, Rodeheffer Matthew S
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Cell Metab. 2016 Jul 12;24(1):142-50. doi: 10.1016/j.cmet.2016.05.012. Epub 2016 Jun 16.
The sexually dimorphic distribution of adipose tissue influences the development of obesity-associated pathologies. The accumulation of visceral white adipose tissue (VWAT) that occurs in males is detrimental to metabolic health, while accumulation of subcutaneous adipose tissue (SWAT) seen in females may be protective. Here, we show that adipocyte hyperplasia contributes directly to the differential fat distribution between the sexes. In male mice, high-fat diet (HFD) induces adipogenesis specifically in VWAT, while in females HFD induces adipogenesis in both VWAT and SWAT in a sex hormone-dependent manner. We also show that the activation of adipocyte precursors (APs), which drives adipocyte hyperplasia in obesity, is regulated by the adipose depot microenvironment and not by cell-intrinsic mechanisms. These findings indicate that APs are plastic cells, which respond to both local and systemic signals that influence their differentiation potential independent of depot origin. Therefore, depot-specific AP niches coordinate adipose tissue growth and distribution.
脂肪组织的性别二态性分布会影响肥胖相关病理的发展。男性体内出现的内脏白色脂肪组织（VWAT）积累对代谢健康有害，而女性体内出现的皮下脂肪组织（SWAT）积累可能具有保护作用。在此，我们表明脂肪细胞增生直接导致了两性之间脂肪分布的差异。在雄性小鼠中，高脂饮食（HFD）特异性地诱导VWAT中的脂肪生成，而在雌性小鼠中，HFD以性激素依赖的方式诱导VWAT和SWAT中的脂肪生成。我们还表明，在肥胖中驱动脂肪细胞增生的脂肪细胞前体（APs）的激活受脂肪储存微环境调节，而非细胞内在机制调节。这些发现表明，APs是可塑性细胞，它们对影响其分化潜能的局部和全身信号作出反应，而与储存部位无关。因此，特定储存部位的AP龛协调脂肪组织的生长和分布。
