TY - JOUR
T1 - MTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold
AU - Labbé, Sébastien M.
AU - Mouchiroud, Mathilde
AU - Caron, Alexandre
AU - Secco, Blandine
AU - Freinkman, Elizaveta
AU - Lamoureux, Guillaume
AU - Gélinas, Yves
AU - Lecomte, Roger
AU - Bossé, Yohan
AU - Chimin, Patricia
AU - Festuccia, William T.
AU - Richard, Denis
AU - Laplante, Mathieu
N1 - Funding Information:
This work was supported by grants from the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), Le Fonds de la Recherche Santé Québec (FRQS), Le Réseau de recherche en santé cardiométabolique, diabète et obésité (CMDO), Le Réseau de bio-imagerie du Québec (RBIQ), Diabète Québec, and La Fondation de l'Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ) to ML. SML is the recipient of a CIHR postdoctoral fellowship. AC held a fellowship from the CIHR Training Program in Obesity/Healthy Body Weight Research and now holds a postdoctoral fellowship from the Canadian Diabetes Association. YB holds a Canada Research Chair in Genomics of Heart and Lung Diseases. WTF hold a grant from FAPESP (2015/19530-5). EF holds a grant from the United States Department of Defense (W81XWH-15-1-0337, Peer-Reviewed Medical Research Program).
Publisher Copyright:
© The Author(s) 2016.
PY - 2016/11/23
Y1 - 2016/11/23
N2 - In response to cold, brown adipose tissue (BAT) increases its metabolic rate and expands its mass to produce heat required for survival, a process known as BAT recruitment. The mechanistic target of rapamycin complex 1 (mTORC1) controls metabolism, cell growth and proliferation, but its role in regulating BAT recruitment in response to chronic cold stimulation is unknown. Here, we show that cold activates mTORC1 in BAT, an effect that depends on the sympathetic nervous system. Adipocyte-specific mTORC1 loss in mice completely blocks cold-induced BAT expansion and severely impairs mitochondrial biogenesis. Accordingly, mTORC1 loss reduces oxygen consumption and causes a severe defect in BAT oxidative metabolism upon cold exposure. Using in vivo metabolic imaging, metabolomics and transcriptomics, we show that mTORC1 deletion impairs glucose and lipid oxidation, an effect linked to a defect in tricarboxylic acid (TCA) cycle activity. These analyses also reveal a severe defect in nucleotide synthesis in the absence of mTORC1. Overall, these findings demonstrate an essential role for mTORC1 in the regulation of BAT recruitment and metabolism in response to cold.
AB - In response to cold, brown adipose tissue (BAT) increases its metabolic rate and expands its mass to produce heat required for survival, a process known as BAT recruitment. The mechanistic target of rapamycin complex 1 (mTORC1) controls metabolism, cell growth and proliferation, but its role in regulating BAT recruitment in response to chronic cold stimulation is unknown. Here, we show that cold activates mTORC1 in BAT, an effect that depends on the sympathetic nervous system. Adipocyte-specific mTORC1 loss in mice completely blocks cold-induced BAT expansion and severely impairs mitochondrial biogenesis. Accordingly, mTORC1 loss reduces oxygen consumption and causes a severe defect in BAT oxidative metabolism upon cold exposure. Using in vivo metabolic imaging, metabolomics and transcriptomics, we show that mTORC1 deletion impairs glucose and lipid oxidation, an effect linked to a defect in tricarboxylic acid (TCA) cycle activity. These analyses also reveal a severe defect in nucleotide synthesis in the absence of mTORC1. Overall, these findings demonstrate an essential role for mTORC1 in the regulation of BAT recruitment and metabolism in response to cold.
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U2 - 10.1038/srep37223
DO - 10.1038/srep37223
M3 - Article
C2 - 27876792
AN - SCOPUS:84996502486
SN - 2045-2322
VL - 6
JO - Scientific reports
JF - Scientific reports
M1 - 37223
ER -