Cardiac natriuretic peptides promote adipose 'browning' through mTOR complex-1.

Liu D, Ceddia RP, Collins S
Mol Metab. 2018 9: 192-198

PMID: 29396369 · PMCID: PMC5870104 · DOI:10.1016/j.molmet.2017.12.017

OBJECTIVE - Activation of thermogenesis in brown adipose tissue (BAT) and the ability to increase uncoupling protein 1 (UCP1) levels and mitochondrial biogenesis in white fat (termed 'browning'), has great therapeutic potential to treat obesity and its comorbidities because of the net increase in energy expenditure. β-adrenergic-cAMP-PKA signaling has long been known to regulate these processes. Recently PKA-dependent activation of mammalian target of rapamycin complex 1 (mTORC1) was shown to be necessary for adipose 'browning' as well as proper development of the interscapular BAT. In addition to cAMP-PKA signaling pathways, cGMP-PKG signaling also promotes this browning process; however, it is unclear whether or not mTORC1 is also necessary for cGMP-PKG induced browning.

METHOD - Activation of mTORC1 by natriuretic peptides (NP), which bind to and activate the membrane-bound guanylyl cyclase, NP receptor A (NPRA), was assessed in mouse and human adipocytes in vitro and mouse adipose tissue in vivo.

RESULTS - Activation of mTORC1 by NP-cGMP signaling was observed in both mouse and human adipocytes. We show that NP-NPRA-PKG signaling activate mTORC1 by direct PKG phosphorylation of Raptor at Serine 791. Administration of B-type natriuretic peptide (BNP) to mice induced Ucp1 expression in inguinal adipose tissue in vivo, which was completely blocked by the mTORC1 inhibitor rapamycin.

CONCLUSION - Our results demonstrate that NP-cGMP signaling activates mTORC1 via PKG, which is a component in the mechanism of adipose browning.

Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

MeSH Terms (15)

Adipose Tissue, Brown Animals Atrial Natriuretic Factor Cells, Cultured Cyclic GMP-Dependent Protein Kinases Female HEK293 Cells Humans Male Mechanistic Target of Rapamycin Complex 1 Mice Mice, Inbred C57BL Mitochondria Signal Transduction Uncoupling Protein 1

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