肥胖所致的脂肪组织慢性炎症是引发糖尿病，心血管疾病等代谢性疾病的重要原因，但肥胖如何驱动脂肪组织慢性炎症具体机制不明。肥胖状态下，脂肪细胞源性外泌体miRNA经旁分泌促进脂肪组织巨噬细胞（ATMs）向M1极化可能是导致脂肪组织慢性炎症的新机制。我们前期发现，高脂饮食诱导的肥胖小鼠脂肪细胞源性外泌体miR-32分泌显著增加，miR-32敲除上调ATMs中KLF4表达，显著改善肥胖小鼠脂肪组织慢性炎症。我们提出科学假说：脂肪细胞源性外泌体miR-32以旁分泌方式靶向负调控KLF4，诱导ATMs向促炎M1型极化，促进肥胖所致的脂肪组织慢性炎症。本项目将结合临床及体内外实验，利用脂肪细胞特异性敲除及过表达小鼠模型，应用KLF4过表达及沉默病毒，明确肥胖状态下，脂肪细胞源性外泌体miR-32能否及如何调节ATMs向M1极化，为防治肥胖所致的脂肪组织慢性炎症提供新的理论依据。

Obesity-induced chronic inflammation in adipose tissue is considered a crucial event for the development of metabolic diseases such as T2DM and cardiovascular diseases. The triggers for obesity-induced chronic adipose tissue inflammation are still poorly defined. Evidences suggest that adipocyte-derived exosomal miRNA could facilitate M1-like macrophages polarization in a paracrine manner, which may be a new mechanism for obesity-induced chronic adipose tissue inflammation. In our previous research, we found that adipocytes derived from epididymal adipose tissue obtained from obese mice released more exosomal miR-32 than adipocytes derived from lean mice. miR-32 knockout up-regulated KLF4 expression in ATMs and significantly improved chronic inflammation of adipose tissue in obese mice. Hence, we hypothesized that adipocyte-derived exosomal miR-32, represents a paracrine signaling system, whereby proinflammatory ATMs may result in obesity-induced chronic adipose tissue inflammation. We will combine clinical and the in vivo/vitro experiments to establish miR-32 knockout/transgenic mice model and KLF4 lentivirus to investigate whether and how the adipocyte-derived exosomal miR-32 can facilitate proinflammatory ATMs during obesity. Thus, our research will provide a new therapeutic target for obesity-induced chronic adipose tissue inflammation.