MTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold

Sébastien M. Labbé, Mathilde Mouchiroud, Alexandre Caron, Blandine Secco, Elizaveta Freinkman, Guillaume Lamoureux, Yves Gélinas, Roger Lecomte, Yohan Bossé, Patricia Chimin, William T. Festuccia, Denis Richard, Mathieu Laplante

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24 Scopus citations

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.

Original languageEnglish (US)
Article number37223
JournalScientific reports
Volume6
DOIs
StatePublished - Nov 23 2016
Externally publishedYes

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    Labbé, S. M., Mouchiroud, M., Caron, A., Secco, B., Freinkman, E., Lamoureux, G., Gélinas, Y., Lecomte, R., Bossé, Y., Chimin, P., Festuccia, W. T., Richard, D., & Laplante, M. (2016). MTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold. Scientific reports, 6, [37223]. https://doi.org/10.1038/srep37223