Mammalian cold TRP channels: impact on thermoregulation and energy homeostasis

  • Rosa Señarís
  • Purificación Ordás
  • Alfonso Reimúndez
  • Félix Viana
Invited Review

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.

Keywords

TRP channels TRPM8 TRPA1 Thermoregulation Obesity 

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

Notes

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.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Departamento de Fisiología, CIMUSUniversidad de Santiago de CompostelaSantiago de CompostelaSpain
  2. 2.Instituto de Neurociencias de AlicanteUniversidad Miguel Hernández-CSICSan Juan de AlicanteSpain

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