DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance.
We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection.
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Quebec, Canada; and Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
Alexandre
A
Caron
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Quebec, Canada; and Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
Sébastien M
SM
Labbé
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Quebec, Canada; and Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
Mathilde
M
Mouchiroud
Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
Renaud
R
Huard
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Quebec, Canada; and Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
Damien
Lanfray
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Quebec, Canada; and Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada.
Denis
D
Richard
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Quebec, Canada; and Département de Médecine, Faculté de Médecine, Université Laval, Québec, Québec, Canada mathieu.laplante@criucpq.ulaval.ca.
Mathieu
M
Laplante
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D007033:Hypothalamus, Middle / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; C570841:deptor protein, mouse; D005947:Glucose
DEPTOR; POMC; energy balance; glucose metabolism; mTOR