RNA-Sequencing analysis of adipose tissue from obese WT mice and AP2-Cre MCT1 knockout mice

Adipose tissue is an active producer of lactate. In obesity, the increased size of adipocytes is accompanied by an increase in lactate production in adipose tissue, caused by hypoxia in obese adipocytes. How lactate affects metabolism in adipocyte and insulin sensitivity remains unclear. Here we develop a mouse model of MCT1,coding by Slc16a1, specific deletion in adipose tissues, using the AP2 promoter to drive Cre expression. This MCT1 AKO mice develop more severe insulin resistance in obesity with 16 weeks high fat diet treatment, while few changes happen to lipid metabolism in adipose tissues. We used RNA-seq to analyze the gene expression patterns of eWAT of obese MCT1 AKO mice compared to WT, and found significant changes in innate immune signaling and adipocyte apoptosis that reflect systemic inflammation and insulin resistance. We analyzed eWAT from 4 obese Slc16a1 flox/flox male mice (WT) and 4 obese AP2-cre Slc16a1 flox/flox male mice(AKO).

脂肪组织是乳酸的活跃产生组织。在肥胖状态下，脂肪细胞体积增大的同时，脂肪组织的乳酸生成量也会升高，该现象由肥胖脂肪细胞的缺氧状态所介导。目前乳酸如何影响脂肪细胞代谢与胰岛素敏感性仍不明确。本研究借助AP2启动子驱动Cre重组酶表达，构建了由Slc16a1编码的单羧酸转运蛋白1（MCT1）脂肪组织特异性敲除小鼠模型。经16周高脂饮食造模后，该MCT1脂肪组织特异性敲除（AKO）小鼠在肥胖状态下表现出更严重的胰岛素抵抗，而其脂肪组织的脂质代谢仅发生微小变化。本研究通过RNA测序（RNA-seq）对比分析肥胖状态下MCT1 AKO小鼠与野生型（WT）小鼠附睾白色脂肪组织（eWAT）的基因表达谱，发现反映全身性炎症与胰岛素抵抗的先天免疫信号通路及脂肪细胞凋亡相关基因表达出现显著改变。本次分析的样本包括4只肥胖的Slc16a1 flox/flox雄性野生型小鼠，以及4只肥胖的AP2-cre Slc16a1 flox/flox雄性MCT1 AKO小鼠。