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Publication
Defective autophagy in Sf1 neurons perturbs the metabolic response to fasting
and causes mitochondrial dysfunction.
Authors Coupé B, Leloup C, Asiedu K, Maillard J, Pénicaud L, Horvath TL, Bouret SG
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Molecular metabolism
Year 2021
Date Published 5/1/2021
Volume : Pages 47 : 101186
PubMed Reference 33571700
Abstract The ventromedial nucleus of the hypothalamus (VMH) is a critical component of
the forebrain pathways that regulate energy homeostasis. It also plays an
important role in the metabolic response to fasting. However, the mechanisms
contributing to these physiological processes remain elusive. Autophagy is an
evolutionarily conserved mechanism that maintains cellular homeostasis by
turning over cellular components and providing nutrients to the cells during
starvation. Here, we investigated the importance of the autophagy-related gene
Atg7 in Sf1-expressing neurons of the VMH in control and fasted conditions., We
generated Sf1-Cre; Atg7loxP/loxP mice and examined their metabolic and cellular
response to fasting., Fasting induces autophagy in the VMH, and mice lacking
Atg7 in Sf1-expressing neurons display altered leptin sensitivity and impaired
energy expenditure regulation in response to fasting. Moreover, loss of Atg7 in
Sf1 neurons causes alterations in the central response to fasting. Furthermore,
alterations in mitochondria morphology and activity are observed in mutant
mice., Together, these data show that autophagy is nutritionally regulated in
VMH neurons and that VMH autophagy participates in the control of energy
homeostasis during fasting.




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