Role of Cathelicidin in Obesity and Diabetes

 描述（由申请方提供）：Cathelicidin（人类中的LL-37和小鼠中的mCRAMP）是具有抗菌功能的内源性肽家族，参与先天免疫应答以保护宿主免受感染。Cathelicidin还表现出抗炎和抗肿瘤作用，并促进糖尿病小鼠的皮肤伤口愈合。尽管凯萨林菌素具有所有这些确定的积极益处，但没有报道显示凯萨林菌素的代谢功能。初步结果显示，血液中的凯萨林菌素水平随着非糖尿病患者的体重指数而增加。在链脲佐菌素治疗的糖尿病小鼠中施用表达凯萨林菌素的慢病毒减少高脂肪诱导的肥胖和肝脂肪变性。Cathelicidin通过降低脂肪受体CD 36表达抑制小鼠和人分化脂肪细胞中的脂肪蓄积。Cathelicidin似乎是一种调节脂肪代谢的代谢激素。这个项目的假设是，cathelicidin抑制 脂肪细胞或肝细胞的脂肪积累通过减少PPARalpha/gamma和CD 36脂肪受体表达。预期慢病毒凯萨林菌素表达减少肥胖糖尿病db/db小鼠的脂肪量和肝脏相关并发症（脂肪性肝炎和肝纤维化）。将确定凯萨林菌素通过使用PPARalpha、PPARgamma和CD 36过表达抑制PPAR家族和CD 36表达来抑制动物脂肪量的作用。将确定凯萨林菌素在人分化的脂肪细胞和肝细胞中通过使用各种药理学和分子方法抑制PPAR家族来抑制脂肪蓄积和/或CD 36表达的作用。血液中的Cathelicidin也可能表明肥胖和糖尿病的严重程度和并发症。将确定肥胖和糖尿病患者中LL-37水平与体重指数、血糖水平、血脂水平和糖尿病并发症等的相关性。这一建议将提供有价值的洞察cathelicidin的作用和机制，作为一个潜在的诊断或治疗肥胖和糖尿病的方法。

 DESCRIPTION (provided by applicant): Cathelicidin (LL-37 in humans and mCRAMP in mice) is a family of endogenous peptides with antimicrobial functions that is involved with innate immune response to protect the host against infection. Cathelicidin also exhibits anti-inflammatory and anti-tumoral effects, and promotes skin wound healing in diabetic mice. Despite all of these determined positive benefits of cathelicidin, there is no report showing the metabolic functions of cathelicidin. Preliminary results have shown that cathelicidin level in the blood increases with body mass index of non-diabetic patients. Administration of cathelicidin expressing lentivirus reduces high fat induced obesity and hepatic steatosis in streptozotocin treated diabetic mice. Cathelicidin inhibits fat accumulation in mouse and human differentiated adipocytes with reduced fat receptor CD36 expression. Cathelicidin appears to be a metabolic hormone that regulates fat metabolism. The hypothesis of this project is that cathelicidin inhibits adipocyte or hepatocyte fat accumulation by reducing PPARalpha/gamma and CD36 fat receptor expression. Lentiviral cathelicidin expression is expected to reduce fat mass and liver related complications (steatohepatitis and liver fibrosis) of obese diabetic db/db mice. The role of cathelicidin in inhibiting fat mass of the animal via inhibiting PPAR family and CD36 expression using PPARalpha, PPARgamma, and CD36 overexpression will be determined. The effect of cathelicidin in inhibiting fat accumulation and/or CD36 expression via PPAR family inhibition using various pharmacological and molecular approaches in human differentiated adipocytes and hepatocytes will be determined. Cathelicidin in the blood may also indicate severity and complications of obesity and diabetes. The correlation of LL-37 levels in obese and diabetic patients with body mass index, blood glucose level, lipid levels and diabetic complications, etc will be determined. This proposal will provide valuable insight to the role and mechanism of cathelicidin as a potential diagnostic or therapeutic approach against obesity and diabetes.