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An exercise-inducible metabolite that suppresses feeding and obesity
Nature ( IF 64.8 ) Pub Date : 2022-06-15 , DOI: 10.1038/s41586-022-04828-5
Veronica L Li 1, 2, 3, 4 , Yang He 5 , Kévin Contrepois 6, 7, 8 , Hailan Liu 5 , Joon T Kim 1, 3 , Amanda L Wiggenhorn 1, 2, 3 , Julia T Tanzo 1, 3 , Alan Sheng-Hwa Tung 1, 3 , Xuchao Lyu 1, 3, 4 , Peter-James H Zushin 9 , Robert S Jansen 10, 11 , Basil Michael 6 , Kang Yong Loh 2, 3 , Andrew C Yang 12 , Christian S Carl 13 , Christian T Voldstedlund 13 , Wei Wei 1, 3, 14 , Stephanie M Terrell 1, 3 , Benjamin C Moeller 15, 16 , Rick M Arthur 16 , Gareth A Wallis 17 , Koen van de Wetering 10, 18 , Andreas Stahl 9 , Bente Kiens 13 , Erik A Richter 13 , Steven M Banik 2, 3 , Michael P Snyder 4, 6, 7, 8 , Yong Xu 5, 19 , Jonathan Z Long 1, 3, 4, 7, 8
Affiliation  

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1,2,3,4,5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance.



中文翻译:

一种运动诱导代谢物,可抑制进食和肥胖

锻炼可以预防肥胖、2 型糖尿病和其他心脏代谢疾病1,2,3,4,5。然而,介导体力活动代谢益处的分子和细胞机制仍不清楚6在这里,我们发现运动可以刺激N-乳酰基苯丙氨酸 (Lac-Phe)的产生,这是一种血源性信号代谢物,可以抑制进食和肥胖。由乳酸和苯丙氨酸生物合成 Lac-Phe 发生在 CNDP2 +细胞中,包括巨噬细胞、单核细胞以及位于不同器官的其他免疫细胞和上皮细胞。在饮食诱导的肥胖小鼠中,药物介导的 Lac-Phe 增加会减少食物摄入量,而不影响运动或能量消耗。长期服用 Lac-Phe 可减少肥胖和体重,并改善葡萄糖稳态。相反,小鼠 Lac-Phe 生物合成的基因消除会增加运动训练后的食物摄入量和肥胖。最后,在人类和赛马中也观察到了循环 Lac-Phe 的大量活动诱导增加,从而确定了这种代谢物作为与跨多种活动模式和哺乳动物物种的身体活动相关的分子效应物。这些数据定义了一种保守的运动诱导代谢物,可以控制食物摄入并影响全身能量平衡。

更新日期:2022-06-16
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