焦虑
内分泌学
内科学
生物
食物摄入量
压力(语言学)
心理学
食品科学
医学
精神科
语言学
哲学
作者
Carla Igual Gil,Bethany M Coull,Wenke Jonas,Rachel N. Lippert,К. Schimrigk,Mario Ost
出处
期刊:Life science alliance
[Life Science Alliance]
日期:2022-09-06
卷期号:5 (11): e202201495-e202201495
被引量:3
标识
DOI:10.26508/lsa.202201495
摘要
Growth differentiation factor 15 (GDF15) is a mitochondrial stress-induced cytokine that modulates energy balance in an endocrine manner. However, the importance of its brainstem-restricted receptor GDNF family receptor alpha-like (GFRAL) to mediate endocrine GDF15 signaling to the brain upon mitochondrial dysfunction is still unknown. Using a mouse model with muscle-specific mitochondrial dysfunction, we here show that GFRAL is required for activation of systemic energy metabolism via daytime-restricted anorexia but not responsible for muscle wasting. We further find that muscle mitochondrial stress response involves a GFRAL-dependent induction of hypothalamic corticotropin-releasing hormone, without elevated corticosterone levels. Finally, we identify that GFRAL signaling governs an anxiety-like behavior in male mice with muscle mitochondrial dysfunction, with females showing a less robust GFRAL-dependent anxiety-like phenotype. Together, we here provide novel evidence of a mitochondrial stress-induced muscle-brain crosstalk via the GDF15-GFRAL axis to modulate food intake and anxiogenic behavior.
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