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Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

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Second messenger signaling mechanisms of the brown adipocyte thermogenic program: an integrative perspective

Fubiao Shi
  • Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL 32827, USA
  • Other articles by this author:
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/ Sheila Collins
  • Corresponding author
  • Integrative Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, 6400 Sanger Road, Orlando, FL 32827, USA
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Published Online: 2017-09-26 | DOI: https://doi.org/10.1515/hmbci-2017-0062

Abstract

β-adrenergic receptors (βARs) are well established for conveying the signal from catecholamines to adipocytes. Acting through the second messenger cyclic adenosine monophosphate (cAMP) they stimulate lipolysis and also increase the activity of brown adipocytes and the ‘browning’ of adipocytes within white fat depots (so-called ‘brite’ or ‘beige’ adipocytes). Brown adipose tissue mitochondria are enriched with uncoupling protein 1 (UCP1), which is a regulated proton channel that allows the dissipation of chemical energy in the form of heat. The discovery of functional brown adipocytes in humans and inducible brown-like (‘beige’ or ‘brite’) adipocytes in rodents have suggested that recruitment and activation of these thermogenic adipocytes could be a promising strategy to increase energy expenditure for obesity therapy. More recently, the cardiac natriuretic peptides and their second messenger cyclic guanosine monophosphate (cGMP) have gained attention as a parallel signaling pathway in adipocytes, with some unique features. In this review, we begin with some important historical work that touches upon the regulation of brown adipocyte development and physiology. We then provide a synopsis of some recent advances in the signaling cascades from β-adrenergic agonists and natriuretic peptides to drive thermogenic gene expression in the adipocytes and how these two pathways converge at a number of unexpected points. Finally, moving from the physiologic hormonal signaling, we discuss yet another level of control downstream of these signals: the growing appreciation of the emerging roles of non-coding RNAs as important regulators of brown adipocyte formation and function. In this review, we discuss new developments in our understanding of the signaling mechanisms and factors including new secreted proteins and novel non-coding RNAs that control the function as well as the plasticity of the brown/beige adipose tissue as it responds to the energy needs and environmental conditions of the organism.

Keywords: β-adrenergic receptor; beige adipocyte; brown adipocyte; long non-coding RNA; microRNA; natriuretic peptide; thermogenesis; uncoupling

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About the article

Received: 2017-08-18

Accepted: 2017-08-29

Published Online: 2017-09-26


Author Statement

Research funding: Authors state no funding involved.

Conflict of interest: Authors state no conflict of interest.

Informed consent: Informed consent is not applicable.

Ethical approval: The conducted research is not related to either human or animals use.


Citation Information: Hormone Molecular Biology and Clinical Investigation, 20170062, ISSN (Online) 1868-1891, DOI: https://doi.org/10.1515/hmbci-2017-0062.

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