美国芝加哥大学Marcelo A. Nóbrega和Grace T. Hansen以及美国明尼苏达大学Ricardo A. Battaglino和Liang Ye共同合作，近期取得重要研究成果。他们最新提出了人类两性脂肪分布的遗传学研究。相关研究成果2023年2月16日在线发表于《自然—遗传学》杂志上。

据介绍，腹部肥胖加剧了肥胖相关的发病率，腹部肥胖可以通过调整体重指数（WHRadjBMI）后的腰臀比来衡量。

研究人员确定了与肥胖和WHRadjBMI相关的基因，并描述了预测调节女性WHRadjBM基因的等位基因敏感增强子。他们发现，在灵长类特异性Alu反转录转座子中，有几个与腰臀比相关的变异体，这些变异体含有与脂肪细胞分化相关的DNA基序。这表明，人类脂肪分布的遗传成分可能涉及逆转录转座子作为脂肪增强子的共同选择。研究人员评估了最强的女性WHRadjBMI相关基因SNX10在脂肪生物学中的作用，确定它是人类脂肪细胞分化和功能所必需的，并参与雌性小鼠（而不是雄性小鼠）饮食诱导的脂肪膨胀。

总之，这一数据确定了女性特定脂肪分布和介导女性代谢功能障碍的基因和调控机制。

附：英文原文

Title: Genetics of sexually dimorphic adipose distribution in humans

Author: Hansen, Grace T., Sobreira, Dbora R., Weber, Zachary T., Thornburg, Alexis G., Aneas, Ivy, Zhang, Li, Sakabe, Noboru J., Joslin, Amelia C., Haddad, Gabriela A., Strobel, Sophie M., Laber, Samantha, Sultana, Farhath, Sahebdel, Faezeh, Khan, Kohinoor, Li, Yang I., Claussnitzer, Melina, Ye, Liang, Battaglino, Ricardo A., Nbrega, Marcelo A.

Issue&Volume: 2023-02-16

Abstract: Obesity-associated morbidity is exacerbated by abdominal obesity, which can be measured as the waist-to-hip ratio adjusted for the body mass index (WHRadjBMI). Here we identify genes associated with obesity and WHRadjBMI and characterize allele-sensitive enhancers that are predicted to regulate WHRadjBMI genes in women. We found that several waist-to-hip ratio-associated variants map within primate-specific Alu retrotransposons harboring a DNA motif associated with adipocyte differentiation. This suggests that a genetic component of adipose distribution in humans may involve co-option of retrotransposons as adipose enhancers. We evaluated the role of the strongest female WHRadjBMI-associated gene, SNX10, in adipose biology. We determined that it is required for human adipocyte differentiation and function and participates in diet-induced adipose expansion in female mice, but not males. Our data identify genes and regulatory mechanisms that underlie female-specific adipose distribution and mediate metabolic dysfunction in women.

DOI: 10.1038/s41588-023-01306-0

Source: https://www.nature.com/articles/s41588-023-01306-0