Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood-brain barrier and directly activates orexigenic AgRP⁺ neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight. In humans, a genetic deficiency in asprosin causes a syndrome characterized by low appetite and extreme leanness; this is phenocopied by mice carrying similar mutations and can be fully rescued by asprosin. Furthermore, we found that obese humans and mice had pathologically elevated concentrations of circulating asprosin, and neutralization of asprosin in the blood with a monoclonal antibody reduced appetite and body weight in obese mice, in addition to improving their glycemic profile. Thus, in addition to performing a glucogenic function, asprosin is a centrally acting orexigenic hormone that is a potential therapeutic target in the treatment of both obesity and diabetes.

中文翻译：

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白脂素是一种中枢作用的促食欲激素。


白脂素是一种最近发现的禁食诱导激素，可促进肝葡萄糖的产生。在这里，我们证明循环中的白脂素穿过血脑屏障，并通过 cAMP 依赖性途径直接激活产生食欲的 AgRP ⁺神经元。这种信号传导以 GABA 依赖性方式抑制下游厌食原阿黑皮素 (POMC) 阳性神经元，从而刺激食欲并促使肥胖和体重累积。在人类中，白脂素的遗传缺陷会导致食欲不振和极度消瘦的综合征。携带类似突变的小鼠表现出这种现象，并且可以被白脂素完全拯救。此外，我们发现肥胖的人和小鼠的循环白脂素浓度病理性升高，并且用单克隆抗体中和血液中的白脂素除了改善其血糖状况外，还降低了肥胖小鼠的食欲和体重。因此，除了发挥生糖功能外，白脂素还是一种中枢作用的食欲激素，是治疗肥胖和糖尿病的潜在治疗靶点。