Effect of exosomes dervied from different adipose tissue on gene expression in 3T3L1 cells under high-low fat diet conditions

Exosomes derived from adipose tissues (AT-Exos) have been identified as a crucialmedium in the transmission of information from adipose tissue to itself and to other organs, including exosomes derived from inguinal white adipose tissue (iWAT-Exos), visceral white adipose tissue (vWAT-Exos) and brown adipose tissue (BAT-Exos). However, the functional differences in depot-specific AT-Exos under obese conditions remain elusive. Here we reported that AT-Exos participated in regulating adipocyte inflammation and metabolic homeostasis. Notably, vWAT-Exos play a critical role in promoting lipid accumulation and inflammation in the development of obesity. Although both are derived from “energy storage” WAT, the biological effects exhibited by iWAT-Exos are far different from those vWAT-Exos. Especially under diet-induced obesity conditions, iWAT-Exos appeared to be BAT-Exo-like, exhibiting an “energy expending” type. Altogether, our data indicated that AT-Exos from different depots have distinct functions and effects on adipocytes metabolism. Overall design: To verify the effects of AT-Exos on metabolic homeostasis in adipocytes, we isolated iWAT-Exos, vWAT-Exos and BAT-Exos from (High fat diet) HFD-fed or (low fat diet) LFD-fed mice and stimulated mature 3T3-L1 adipocytes. We then performed gene expression profiling analysis using data obtain from RNA-seq of 7 different cells. Comparative gene expression profiling analysis of RNA-seq data for 3T3L1 cells control group and its treatment group (LFD-iWAT-Exos, LFD-vWAT-Exos, LFD-BAT-Exos, HFD-iWAT-Exos, HFD-vWAT-Exos and HFD-BAT-Exos). Comparative gene expression profiling analysis of RNA-seq data for 3T3L1 cells treated with LFD-AT-Exos and 3T3L1 cells treated with HFD-AT-Exos.

脂肪组织来源外泌体（Adipose Tissue-derived Exosomes，AT-Exos）已被证实是脂肪组织向自身及其他器官传递信息的关键媒介，涵盖腹股沟白色脂肪组织来源外泌体（inguinal White Adipose Tissue-derived Exosomes，iWAT-Exos）、内脏白色脂肪组织来源外泌体（visceral White Adipose Tissue-derived Exosomes，vWAT-Exos）与棕色脂肪组织来源外泌体（Brown Adipose Tissue-derived Exosomes，BAT-Exos）。然而，肥胖状态下不同脂肪库特异性AT-Exos的功能差异仍有待阐明。本研究证实，AT-Exos参与调控脂肪细胞炎症反应与代谢稳态。值得关注的是，vWAT-Exos在肥胖发生进程中对脂质蓄积及炎症反应具有关键促进作用。尽管二者均来源于"储能型"白色脂肪组织，iWAT-Exos所展现的生物学效应却与vWAT-Exos大相径庭。尤其在饮食诱导肥胖状态下，iWAT-Exos呈现出类似BAT-Exos的"耗能型"表型。综上，本研究数据表明，不同脂肪库来源的AT-Exos功能迥异，且对脂肪细胞代谢具有差异化调控效应。

总体实验设计：为验证AT-Exos对脂肪细胞代谢稳态的调控效应，本研究从高脂饮食（High Fat Diet，HFD）或低脂饮食（Low Fat Diet，LFD）喂养的小鼠体内分离提取iWAT-Exos、vWAT-Exos及BAT-Exos，随后以其刺激成熟3T3-L1脂肪细胞。后续通过7组细胞的RNA测序（RNA-seq）数据开展基因表达谱分析，具体包括：对3T3-L1脂肪细胞对照组与各处理组（LFD-iWAT-Exos、LFD-vWAT-Exos、LFD-BAT-Exos、HFD-iWAT-Exos、HFD-vWAT-Exos及HFD-BAT-Exos）的RNA-seq数据进行比较基因表达谱分析；以及对经LFD来源AT-Exos处理的3T3-L1脂肪细胞与经HFD来源AT-Exos处理的3T3-L1脂肪细胞的RNA-seq数据开展比较基因表达谱分析。