TY - JOUR
T1 - DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance
AU - Caron, Alexandre
AU - Labbé, Sébastien M.
AU - Mouchiroud, Mathilde
AU - Huard, Renaud
AU - Lanfray, Damien
AU - Richard, Denis
AU - Laplante, Mathieu
N1 - Publisher Copyright:
© 2016 the American Physiological Society.
PY - 2016/6
Y1 - 2016/6
N2 - 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.
AB - 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.
KW - DEPTOR
KW - Energy balance
KW - Glucose metabolism
KW - POMC
KW - mTOR
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UR - http://www.scopus.com/inward/citedby.url?scp=84984806980&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00549.2015
DO - 10.1152/ajpregu.00549.2015
M3 - Article
C2 - 27097662
AN - SCOPUS:84984806980
SN - 0363-6119
VL - 310
SP - R1322-R1331
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 11
ER -