Paternal cold exposure enhances brown adipose tissue sensitivity in offspring and ameliorates diet induced obesity

Research in recent years has focused on environmental effects that control tissue functionality and systemic metabolism. We show here in a retrospective analysis that presence of brown adipocytes and date of birth are correlated and linked to BMI. In a mouse model system, we demonstrate that pre-conception cold exposure leads to improved systemic metabolism and protects from diet induced obesity, through the sperm via the paternal lineage. Using a brown fat ablation model, we show that this effect is mediated by brown adipose tissue. Furthermore, through RNAseq and DNA methylation analysis we identify Adrb3 as a putative signaling mechanism which could mediate the effects of pre-conception cold exposure and could account for the heterogeneity of brown adipose tissue responsiveness. Taken together, our results identify paternal cold exposure as a stimulus which induces a hyper-active state in brown adipose tissue leading to improved adaptation to overnutrition and hypothermia in the offspring. WGBS-seq of sperm from control and cold stimulated mice

近年来，诸多研究聚焦于调控组织功能与系统代谢的环境影响因子。本研究通过回顾性分析（retrospective analysis）发现，棕色脂肪细胞（brown adipocytes）的存在状态与出生日期及身体质量指数（BMI）存在显著关联。在小鼠模型体系（mouse model system）中，本研究证实，孕前冷暴露（pre-conception cold exposure）可通过父系谱系的精子实现信号传递，改善子代的系统代谢水平并抵御饮食诱导性肥胖（diet-induced obesity）。本研究采用棕色脂肪消融模型（brown fat ablation model），证实该效应由棕色脂肪组织（brown adipose tissue）所介导。此外，本研究通过RNA测序（RNA-seq）与DNA甲基化（DNA methylation）分析，鉴定Adrb3为潜在信号通路机制，其既可介导孕前冷暴露产生的相关效应，也可解释棕色脂肪组织反应性的异质性。综上所述，本研究结果证实，父系冷暴露可作为一种刺激因子，诱导棕色脂肪组织处于高活性状态，从而提升子代对营养过剩与低体温的适应能力。对照组与冷刺激小鼠的精子全基因组亚硫酸氢盐测序（WGBS-seq）