Adipose ILC2s depend on acetyl-CoA carboxylase 1 to maintain metabolic health

IF 37 1区生物学 Q1 CELL BIOLOGY

Cell metabolism Pub Date : 2026-09-23 DOI:10.1016/j.cmet.2026.08.019

Fotios Karagiannis,Maria Rafailia Theodorou,Fabian Nikolka,Maria Doverman,Dhruvi Shah,Chantal Wientjens,Timothy R. McCulloch,Ronja Kardinal,David Colon,Jelena Zurkovic,Jiangyan Yu,Julia Anna Noras,Patricia Weiss,Roman Rombo,Tim Sparwasser,Zeinab Abdullah,Felix Meissner,Christoph Thiele,Jan Hasenauer,Dagmar Wachten,Karsten Hiller,Christoph Wilhelm

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引用次数: 0

Abstract

Adipose group 2 innate lymphoid cells (ILC2s) are essential to maintain metabolic homeostasis. Obesity severely impairs the number and function of ILC2s, resulting in the progression of metabolic inflammation. How ILC2s are perturbed in obesity remains unknown. Here, we find that high-fat diet (HFD)-induced obesity in mice increases fatty acid oxidation, leading to suppression of acetyl-coenzyme A (CoA) carboxylase 1 (ACC1) in adipose ILC2s. ACC1 is essential for maintaining the citrate shuttle, NAD+/NADH balance, and cellular metabolism. Mimicking the effects of HFD, ACC1 deletion impairs differentiation, maintenance, and function of ILC2s. This results in adipose tissue hypertrophy and inflammation at steady state, predisposing mice to the development of diabetes. Supplementing with the NAD+ precursor nicotinamide riboside rescues ACC1 deficiency, restoring ILC2 function and adipose tissue homeostasis. These findings establish ACC1 as a critical regulator of adipose ILC2 maintenance and function and provide a rationale for the adverse effects of ACC inhibition in obesity.

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脂肪ILC2s依赖于乙酰辅酶a羧化酶1来维持代谢健康

脂肪2组先天淋巴样细胞（ILC2s）对维持代谢稳态至关重要。肥胖严重损害ILC2s的数量和功能，导致代谢性炎症的进展。ILC2s如何在肥胖中受到干扰仍然未知。在这里，我们发现高脂肪饮食（HFD）诱导的小鼠肥胖增加脂肪酸氧化，导致脂肪ILC2s中乙酰辅酶A （CoA）羧化酶1 （ACC1）的抑制。ACC1对维持柠檬酸穿梭、NAD+/NADH平衡和细胞代谢至关重要。与HFD类似，ACC1缺失会损害ILC2s的分化、维持和功能。这导致脂肪组织肥大和稳定状态下的炎症，使小鼠易患糖尿病。补充NAD+前体烟酰胺核苷可修复ACC1缺陷，恢复ILC2功能和脂肪组织稳态。这些发现证实了ACC1是脂肪ILC2维持和功能的关键调节因子，并为ACC抑制在肥胖中的不良影响提供了理论依据。

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来源期刊

Cell metabolism 生物-内分泌学与代谢

CiteScore

48.60

自引率

1.40%

发文量

173

审稿时长

2.5 months

期刊介绍： Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others. Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.