| First Author | Igual Gil C | Year | 2022 |
| Journal | Life Sci Alliance | Volume | 5 |
| Issue | 11 | PubMed ID | 36271504 |
| Mgi Jnum | J:348827 | Mgi Id | MGI:7643996 |
| Doi | 10.26508/lsa.202201495 | Citation | Igual Gil C, et al. (2022) Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior. Life Sci Alliance 5(11) |
| abstractText | 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. |
