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Mammalian cold TRP channels: impact on thermoregulation and energy homeostasis

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Abstract

Body temperature regulation is a fundamental homeostatic function in homeothermic animals. It is governed by the central nervous system that integrates temperature signals from internal body structures and the skin and provides efferent responses to adjust heat-exchange rates with the environment. Thermoregulation has a major influence on energy balance by regulating food intake as well as heat production and energy expenditure. Surprisingly, although almost 50% of our energy expenditure is dedicated to maintaining homeothermy, very little is yet known about the molecular aspects and the neural wiring involved in the intimate interrelationship between these two critical homeostatic systems. Some non-selective cation channels of the transient receptor potential (TRP) family work as molecular thermal sensors in sensory neurons and other cells. In this review, we discuss recent advances in our understanding of the basic mechanisms responsible for thermoregulation in the cold. We have focused our attention on the role of two cold-activated TRP channels (transient receptor potential melastatin 8 and transient receptor potential ankyrin 1) in body temperature regulation as well as their impact on energy balance and metabolism. A better understanding of the mechanisms coupling thermoregulation to energy homeostasis, including the involvement of thermosensitive TRPs, may uncover additional mechanisms underlying the pathogenesis of obesity and its metabolic consequences in humans, opening new strategies for the diagnosis, treatment, and prevention of this disease.

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Abbreviations

ATP:

Adenosine triphosphate

BAT:

Brown adipose tissue

BDNF:

Brain-derived neurotrophic factor

BMR:

Basal metabolic rate

cAMP:

Cyclic adenosine monophosphate

CGRP:

Calcitonin gene-related peptide

COX:

Cyclooxygenase

Cryo-EM:

Cryo-electron microscopy

DM:

Dorsomedial

HFD:

High-fat diet

KO:

Knockout

PKA:

Protein kinase A

POA:

Preoptic area

ROS:

Reactive oxygen species

Tc:

Core body temperature

TH:

Tyrosine hydroxylase

TNZ:

Thermoneutral zone

TRP:

Transient receptor potential

TRPA1:

Transient receptor potential ankyrin 1

TRPM2:

Transient receptor potential melastatin 2

TRPM8:

Transient receptor potential melastatin 8

UCP1:

Uncoupling protein 1

WAT:

White adipose tissue

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Acknowledgements

We thank Stuart Ingham for the help with the illustrations, and the members of our laboratories for contributing to the experimental work and participating in fruitful discussions.

Conflict of interest

The authors declare that they have no competing interests.

Funding

The study was supported by projects MINECO SAF2009-11175 (RS) and SAF2016-77233-R (FV) and by the Instituto de Salud Carlos III PI12/0058 (RS) and was cofinanced by the European Regional Development Fund (ERDF) and the Severo Ochoa Programme for Centres of Excellence in R&D (ref. SEV-2013-0317). PO held a predoctoral fellowship MINECO (BES-2011-047063).

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  1. Departamento de Fisiología, CIMUS, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain

    Rosa Señarís & Alfonso Reimúndez

  2. Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550, San Juan de Alicante, Spain

    Purificación Ordás & Félix Viana

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  1. Rosa Señarís
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  2. Purificación Ordás
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  3. Alfonso Reimúndez
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  4. Félix Viana
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Correspondence to Félix Viana.

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This article is part of the special issue on Thermal Biology in Pflügers Archiv - European Journal of Physiology

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Señarís, R., Ordás, P., Reimúndez, A. et al. Mammalian cold TRP channels: impact on thermoregulation and energy homeostasis. Pflugers Arch - Eur J Physiol 470, 761–777 (2018). https://doi.org/10.1007/s00424-018-2145-9

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