Activation of mTORC1 is essential for β-adrenergic stimulation of adipose browning

Mar 29, 2016The Journal of clinical investigation

Activation of mTORC1 is required for fat browning triggered by beta-adrenergic signals

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Abstract

Activation of the p70 ribosomal S6 kinase (S6K1) through mTORC1 is triggered by PKA activation in both mouse and human fat cells.

  • Insulin is known to promote energy storage, while catecholamines stimulate the release of energy from fat.
  • Mice with impaired mTORC1 signaling did not show the expected increase in uncoupling protein UCP1 expression or browning of white adipose tissue when stimulated by β-adrenergic receptors.
  • PKA directly phosphorylated mTOR and RAPTOR, affecting S6K1 activation independently of insulin signaling.
  • Disruption of the PKA site on RAPTOR hindered βAR/mTORC1 activation of S6K1, but did not interfere with insulin-induced mTORC1 activation.
  • A phosphomimetic version of RAPTOR increased S6K1 activity, suggesting a regulatory role in adipose browning.

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