重庆大学Rui Huang和深圳湾实验室Liming Wang研究组合作取得一项新突破。他们的最新研究发现果蝇和小鼠中膳食半胱氨酸通过FMRFamide信号传导驱动体内脂肪减少。相关论文于2023年4月13日发表在《细胞研究》杂志上。

研究人员发现富含蛋白质的饮食明显减少果蝇体内的脂肪储存，这很大程度上与饮食中半胱氨酸的摄入量有关。从机制上讲，膳食半胱氨酸增加了神经肽FMRFamide（FMRFa）的产生。增强的FMRFa活性通过其同源受体（FMRFaR）促进能量消耗并抑制食物摄入，两者都有助于减脂。在脂肪体中，FMRFa信号通过增加PKA和脂肪酶活性来促进脂肪分解。在甜味感知味觉神经元中，FMRFa信号抑制了食欲感知，从而抑制了食物摄入。

研究还发现，膳食半胱氨酸通过神经肽FF（NPFF）信号传导（一种哺乳动物RFamide肽）在小鼠中以类似的方式起作用。

此外，膳食半胱氨酸或FMRFa/NPFF给药对没有行为异常果蝇和小鼠的代谢应激提供了保护作用。因此，该研究揭示了针对肥胖和相关代谢疾病安全有效的治疗新靶点。

据悉，肥胖对全球人口的健康构成威胁，需要安全有效的治疗方案。

附：英文原文

Title: Dietary cysteine drives body fat loss via FMRFamide signaling in Drosophila and mouse

Author: Song, Tingting, Qin, Wusa, Lai, Zeliang, Li, Haoyu, Li, Daihan, Wang, Baojia, Deng, Wuquan, Wang, Tingzhang, Wang, Liming, Huang, Rui

Issue&Volume: 2023-04-13

Abstract: Obesity imposes a global health threat and calls for safe and effective therapeutic options. Here, we found that protein-rich diet significantly reduced body fat storage in fruit flies, which was largely attributed to dietary cysteine intake. Mechanistically, dietary cysteine increased the production of a neuropeptide FMRFamide (FMRFa). Enhanced FMRFa activity simultaneously promoted energy expenditure and suppressed food intake through its cognate receptor (FMRFaR), both contributing to the fat loss effect. In the fat body, FMRFa signaling promoted lipolysis by increasing PKA and lipase activity. In sweet-sensing gustatory neurons, FMRFa signaling suppressed appetitive perception and hence food intake. We also demonstrated that dietary cysteine worked in a similar way in mice via neuropeptide FF (NPFF) signaling, a mammalian RFamide peptide. In addition, dietary cysteine or FMRFa/NPFF administration provided protective effect against metabolic stress in flies and mice without behavioral abnormalities. Therefore, our study reveals a novel target for the development of safe and effective therapies against obesity and related metabolic diseases.

DOI: 10.1038/s41422-023-00800-8

Source: https://www.nature.com/articles/s41422-023-00800-8