GDF15 links adipose tissue lipolysis with anxiety

IF 18.9 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism Pub Date : 2025-04-15 DOI:10.1038/s42255-025-01264-3

Logan K. Townsend, Dongdong Wang, Carly M. Knuth, Russta Fayyazi, Ahmad Mohammad, Léa J. Becker, Evangelia E. Tsakiridis, Eric M. Desjardins, Zeel Patel, Celina M. Valvano, Junfeng Lu, Alice E. Payne, Ofure Itua, Kyle D. Medak, Daniel M. Marko, Jonathan D. Schertzer, David C. Wright, Shawn M. Beaudette, Katherine M. Morrison, André C. Carpentier, Denis P. Blondin, Rebecca E. K. MacPherson, Jordan G. McCall, Marc G. Jeschke, Gregory R. Steinberg

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Abstract

Psychological stress changes both behaviour and metabolism to protect organisms. Adrenaline is an important driver of this response. Anxiety correlates with circulating free fatty acid levels and can be alleviated by a peripherally restricted β-blocker, suggesting a peripheral signal linking metabolism with behaviour. Here we show that adrenaline, the β3 agonist CL316,243 and acute restraint stress induce growth differentiation factor 15 (GDF15) secretion in white adipose tissue of mice. Genetic inhibition of adipose triglyceride lipase or genetic deletion of β-adrenergic receptors blocks β-adrenergic-induced increases in GDF15. Increases in circulating GDF15 require lipolysis-induced free fatty acid stimulation of M2-like macrophages within white adipose tissue. Anxiety-like behaviour elicited by adrenaline or restraint stress is eliminated in mice lacking the GDF15 receptor GFRAL. These data provide molecular insights into the mechanisms linking metabolism and behaviour and suggest that inhibition of GDF15–GFRAL signalling might reduce acute anxiety.

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GDF15将脂肪组织脂解与焦虑联系起来

心理压力会改变行为和新陈代谢，从而保护生物体。肾上腺素是这种反应的重要驱动因素。焦虑与循环游离脂肪酸水平相关，可通过外周限制性β受体阻滞剂缓解，这表明外周信号将代谢与行为联系起来。本研究表明肾上腺素、β3激动剂CL316,243和急性抑制应激可诱导小鼠白色脂肪组织中生长分化因子15 （GDF15）的分泌。脂肪甘油三酯脂肪酶的遗传抑制或β-肾上腺素能受体的遗传缺失可阻断β-肾上腺素能诱导的GDF15的增加。循环GDF15的增加需要脂解诱导的游离脂肪酸刺激白色脂肪组织中的m2样巨噬细胞。在缺乏GDF15受体GFRAL的小鼠中，肾上腺素或约束压力引起的焦虑样行为被消除。这些数据提供了有关代谢和行为联系机制的分子见解，并表明抑制GDF15-GFRAL信号可能会减少急性焦虑。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

27.50

自引率

2.40%

发文量

170

期刊介绍： Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.