皮肤是人体最大的器官，我们前期研究发现皮下脂肪对皮肤抵抗细菌入侵起着重要的天然免疫防护作用，在细菌感染过程中真皮纤维化细胞大量扩增，并分化为脂肪细胞，分化中的不成熟脂肪细胞通过释放抗菌多肽快速有效地抑制细菌生长。肥胖是现在日益严重的社会问题，同时是诱发多种皮肤疾病的风险因素，包括皮下和软组织感染，伤口不愈合溃烂，银屑病等等，但其中机制还不清楚。这里我们假设肥胖会导致皮内脂肪抗菌防护功能丢失从而降低皮肤的天然免疫抗菌力。因此，本课题将研究三个科学问题：1.纤维化细胞和脂肪细胞功能在肥胖后有什么改变？2.肥胖后趋于成熟的脂肪细胞是否通过释放分泌因子例如TGFB来抑制成纤维化细胞的脂肪分化功能？3.通过调节成纤维化细胞分化功能或抑制成熟脂肪细胞能否有效治疗肥胖引发的皮肤抗菌免疫低下问题？这个课题的研究成果将帮助了解肥胖如何影响皮肤的天然免疫系统，对治疗由肥胖引发的皮肤病提供新的靶点和思路。

Skin is the largest organ of our human body, and previously our group has found that dermal fat plays an essential role in skin innate immune defense against bacterial infection. During skin infection, dermal fibroblasts rapidly proliferate, and differentiate into immature adipocytes, which then secret abundant amount of antimicrobial peptide to rapidly and effectively control bacterial growth. Obesity has become a serious health problem around the world and in China, and it is a risk factor for several skin diseases, including skin and soft tissue infections, delayed wound healing and ulceration and psoriasis, but mechanisms underlying these risks upon obesity is still unclear. Here we hypothesize that obesity leads to the loss of antimicrobial protective function of dermal fat and therefore it impairs skin’s innate immune defense function against bacteria. To test this hypothesis, we have proposed 3 aims as shown below: 1. Define the phenotypic and functional changes in dermal fibroblasts and fat upon diet-induced obesity. 2. Determine the mechanisms by which mature fat cells inhibit the adipogenic and antimicrobial of dermal fibroblasts in obesity. 3. Determine whether the innate defense function of obese skin can be restored by enabling the adipogenic and antimicrobial function of dermal fat. The research results of this project will reveal novel mechanisms for how obesity impairs the innate antimicrobial function of dermal fat and how that influences that innate immune system of the skin. This study may also open new therapeutic avenues for improving the global burden of S. aureus skin infection as compounded by the obesity epidemic.