Sex differences in adipose tissue distribution and function are associated with sex differences in cardiometabolic disease. While many studies have revealed sex differences in adipocyte cell signaling and physiology, there is a relative dearth of information regarding sex differences in transcript abundance and regulation. We investigated sex differences in subcutaneous adipose tissue transcriptional regulation using omic-scale data from ∼3000 geographically and ethnically diverse human samples. We identified 162 genes with robust sex differences in expression. Differentially expressed genes were implicated in oxidative phosphorylation and adipogenesis. We further determined that sex differences in gene expression levels could be related to sex differences in the genetics of gene expression regulation. Our analyses revealed sex-specific genetic associations, and this finding was replicated in a study of 98 inbred mouse strains. The genes under genetic regulation in human and mouse were enriched for oxidative phosphorylation and adipogenesis. Enrichment analysis showed that the associated genetic loci resided within binding motifs for adipogenic transcription factors (e.g., PPARG and EGR1). We demonstrated that sex differences in gene expression could be influenced by sex differences in genetic regulation for six genes (e.g., FADS1 and MAP1B). These genes exhibited dynamic expression patterns during adipogenesis and robust expression in mature human adipocytes. Our results support a role for adipogenesis-related genes in subcutaneous adipose tissue sex differences in the genetic and environmental regulation of gene expression.

中文翻译：

---

人类脂肪组织基因表达和遗传调控的性别差异涉及脂肪生成。

脂肪组织分布和功能的性别差异与心脏代谢疾病的性别差异有关。虽然许多研究揭示了脂肪细胞信号传导和生理学方面的性别差异，但关于转录丰度和调节方面的性别差异的信息相对缺乏。我们使用来自约 3000 个不同地域和种族的人类样本的组学规模数据研究了皮下脂肪组织转录调控的性别差异。我们确定了 162 个在表达上具有明显性别差异的基因。差异表达的基因与氧化磷酸化和脂肪形成有关。我们进一步确定基因表达水平的性别差异可能与基因表达调控遗传学的性别差异有关。我们的分析揭示了性别特异性遗传关联，这一发现在对 98 种近交小鼠品系的研究中得到了重复。人类和小鼠中受遗传调控的基因在氧化磷酸化和脂肪形成方面得到了丰富。富集分析表明，相关的基因位点位于脂肪形成转录因子（例如 PPARG 和 EGR1）的结合基序内。我们证明了基因表达的性别差异可能受到六个基因遗传调控性别差异的影响（例如，富集分析表明，相关的基因位点位于脂肪形成转录因子（例如 PPARG 和 EGR1）的结合基序内。我们证明了基因表达的性别差异可能受到六个基因遗传调控性别差异的影响（例如，富集分析表明，相关的基因位点位于脂肪形成转录因子（例如 PPARG 和 EGR1）的结合基序内。我们证明了基因表达的性别差异可能受到六个基因遗传调控性别差异的影响（例如，FADS1和MAP1B）。这些基因在脂肪形成过程中表现出动态表达模式，并在成熟的人类脂肪细胞中表现出强劲的表达。我们的结果支持皮下脂肪组织性别差异中脂肪形成相关基因在基因表达的遗传和环境调控中的作用。