Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, 375 Congress Ave, New Haven, CT 06520, USA; Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University, New Haven, CT, USA.
Department of Comparative Medicine, Yale University School of Medicine, 375 Congress Ave, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT, USA; Yale Stem Cell Center, Yale University, New Haven, CT, USA; Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University, New Haven, CT, USA.
Stem Cell Reports. 2022 May 10;17(5):1081-1088. doi: 10.1016/j.stemcr.2022.04.001. Epub 2022 Apr 28.
Fat distribution is sexually dimorphic and is associated with metabolic disease risk. It is unknown if prepubertal sex-hormone signaling influences adult fat distribution. Here, we show that karyotypically male androgen-insensitive mice exhibit pronounced subcutaneous adiposity compared with wild-type males and females. This subcutaneous adipose bias emerges prior to puberty and is not due to differences in adipocyte size or rates of adipogenesis between visceral and subcutaneous fat. Instead, we find that androgen-insensitive mice lack an adequate progenitor pool for normal visceral-fat expansion during development, thus increasing the subcutaneous-to-visceral-fat ratio. Obesogenic visceral-fat expansion is likewise inhibited in these mice, yet their metabolic health is similar to wild-type animals with comparable total fat mass. Taken together, these data show that adult fat distribution can be determined prior to the onset of puberty by the relative number of progenitors that seed nascent adipose depots.
脂肪分布存在性别二态性，并与代谢疾病风险相关。尚不清楚青春期前的性激素信号是否会影响成年后的脂肪分布。本研究显示，与野生型雌雄小鼠相比，核型为雄性的雄激素不敏感小鼠表现出明显的皮下脂肪堆积。这种皮下脂肪偏向性在青春期前出现，并非由于内脏脂肪和皮下脂肪之间的脂肪细胞大小或脂肪生成率的差异所致。相反，我们发现雄激素不敏感小鼠在发育过程中缺乏正常内脏脂肪扩张所需的足够祖细胞池，从而增加了皮下脂肪与内脏脂肪的比例。这些小鼠的肥胖型内脏脂肪扩张同样受到抑制，但它们的代谢健康与具有相似总脂肪量的野生型动物相似。综上所述，这些数据表明，成年后的脂肪分布可以在青春期前通过形成新生脂肪储存的祖细胞的相对数量来决定。
