Baker Heart & Diabetes Institute, Melbourne, VIC, Australia, 3004.
Central Clinical School, Monash University, Melbourne, VIC, Australia, 3004.
Nat Commun. 2021 Jan 4;12(1):74. doi: 10.1038/s41467-020-20434-3.
The effective storage of lipids in white adipose tissue (WAT) critically impacts whole body energy homeostasis. Many genes have been implicated in WAT lipid metabolism, including tripartite motif containing 28 (Trim28), a gene proposed to primarily influence adiposity via epigenetic mechanisms in embryonic development. However, in the current study we demonstrate that mice with deletion of Trim28 specifically in committed adipocytes, also develop obesity similar to global Trim28 deletion models, highlighting a post-developmental role for Trim28. These effects were exacerbated in female mice, contributing to the growing notion that Trim28 is a sex-specific regulator of obesity. Mechanistically, this phenotype involves alterations in lipolysis and triglyceride metabolism, explained in part by loss of Klf14 expression, a gene previously demonstrated to modulate adipocyte size and body composition in a sex-specific manner. Thus, these findings provide evidence that Trim28 is a bona fide, sex specific regulator of post-developmental adiposity and WAT function.
白色脂肪组织（WAT）中脂质的有效储存对全身能量稳态具有重要影响。许多基因都与 WAT 脂质代谢有关，包括三结构域包含蛋白 28（Trim28），该基因被认为主要通过胚胎发育过程中的表观遗传机制影响肥胖。然而，在本研究中，我们证明了在已分化的脂肪细胞中特异性缺失 Trim28 的小鼠也会像全身缺失 Trim28 模型一样发生肥胖，这突出了 Trim28 在发育后的作用。这种影响在雌性小鼠中更为严重，这进一步证明了 Trim28 是肥胖的性别特异性调节因子。从机制上讲，这种表型涉及脂肪分解和甘油三酯代谢的改变，部分原因是 Klf14 表达的丧失，先前的研究表明该基因以性别特异性的方式调节脂肪细胞大小和身体成分。因此，这些发现为 Trim28 是一种真正的、性别特异性的发育后肥胖和 WAT 功能调节剂提供了证据。
