title: mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold.
abstract: 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.
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, 2725 chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Sébastien M
authors.initials: SM
authors.lastname: Labbé
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, 2725 chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Mouchiroud
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, 2725 chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Caron
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, 2725 chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Blandine
authors.initials: B
authors.lastname: Secco
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Freinkman
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, 2725 chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lamoureux
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, 2725 chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Gélinas
authors.affiliation: Centre d'imagerie moléculaire de Sherbrooke (CIMS), Département de Médecine nucléaire et radiobiologie, Université de Sherbrooke, Sherbrooke, J1H 5N4, Canada.
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, 2725 chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Department of Physiology &Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-000, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Chimin
authors.affiliation: Department of Physiology &Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-000, Brazil.
authors.forename: William T
authors.initials: WT
authors.lastname: Festuccia
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, 2725 chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, 2725 chemin Sainte-Foy, Québec, QC, G1V 4G5, Canada.|Département de Médecine, Faculté de Médecine, Université Laval, Québec, QC, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Laplante
mesh_terms: D000064:Acclimatization / Q000502:physiology*; D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D003080:Cold Temperature; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology
chemical_list: D000076222:Mechanistic Target of Rapamycin Complex 1