mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold

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Labbe, Sebastien M. ; Mouchiroud, Mathilde ; Caron, Alexandre ; Secco, Blandine ; Freinkman, Elizaveta ; Lamoureux, Guillaume ; Gelinas, Yves ; Lecomte, Roger ; Bosse, Yohan ; Chimin, Patricia ; Festuccia, William T. ; Richard, Denis ; Laplante, Mathieu

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 6, NOV 23 2016.
• Citações Web of Science: 11

Resumo

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. (AU)

• Processo FAPESP: 15/19530-5 - Caracterização do envolvimento do sensor de nutrientes mTOR no desenvolvimento de doenças metabólicas crônicas associadas à obesidade
• Beneficiário: William Tadeu Lara Festuccia
• Modalidade de apoio: Auxílio à Pesquisa - Temático