Mammalian cold TRP channels: impact on thermoregulation and energy homeostasis

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


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.


TRP channels TRPM8 TRPA1 Thermoregulation Obesity 



Adenosine triphosphate


Brown adipose tissue


Brain-derived neurotrophic factor


Basal metabolic rate


Cyclic adenosine monophosphate


Calcitonin gene-related peptide




Cryo-electron microscopy




High-fat diet




Protein kinase A


Preoptic area


Reactive oxygen species


Core body temperature


Tyrosine hydroxylase


Thermoneutral zone


Transient receptor potential


Transient receptor potential ankyrin 1


Transient receptor potential melastatin 2


Transient receptor potential melastatin 8


Uncoupling protein 1


White adipose tissue



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 information

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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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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