Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production

Marco Rossato; Marnie Granzotto; Veronica Macchi; Andrea Porzionato; Lucia Petrelli; Alessandra Calcagno; Juri Vencato; Diego De Stefani; Valentina Silvestrin; Rosario Rizzuto; Franco Bassetto; Raffaele De Caro; Roberto Vettor

doi:10.1016/j.mce.2013.12.005

Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production

Mol Cell Endocrinol. 2014 Mar 5;383(1-2):137-46. doi: 10.1016/j.mce.2013.12.005. Epub 2013 Dec 14.

Affiliations

¹ Department of Medicine - DIMED, Clinica Medica 3, School of Medicine, University of Padova, Padova, Italy. Electronic address: marco.rossato@unipd.it.
² Department of Medicine - DIMED, Clinica Medica 3, School of Medicine, University of Padova, Padova, Italy.
³ Department of Molecular Medicine, Section of Anatomy, School of Medicine, University of Padova, Padova, Italy.
⁴ Department of Animal Medicine, Production and Health, University of Padova, Padova, Italy.
⁵ Department of Biomedical Sciences, School of Medicine, University of Padova, Padova, Italy.
⁶ Department of Neurosciences, Plastic Surgery Clinic, University of Padova, Padova, Italy.

PMID: 24342393
DOI: 10.1016/j.mce.2013.12.005

Abstract

Mammals possess two types of adipose tissue, white (WAT) and brown (BAT). The uncoupling protein 1 (UCP1) is a hallmark of BAT, being the pivotal player for cold-induced thermogenesis. WAT can acquire BAT characteristics with up-regulation of UCP1 after cold exposure or adrenergic stimulation. In the present study we demonstrated that human white adipocytes express the cold-sensing receptor TRPM8 which activation by menthol and icilin induced a rise in [Ca²⁺](i) and UCP1 expression, increased mitochondrial membrane potential, glucose uptake and heat production. The induction of "brown-like" phenotype in human white adipocytes after TRPM8 activation was supported by ultrastructural morphological changes of mitochondrial morphology and of their intracellular localization, with no modifications of the genes regulating mitochondrial biogenesis. In conclusion human white adipocytes express the cold receptor TRPM8 which activation induces their "browning" supporting a possible role of this receptor in the control of adipose tissue metabolism and body energy balance.

Keywords: Human adipocyte; Menthol; Mitochondria; TRPM8; UCP1.

MeSH terms

Adipocytes, White / cytology
Adipocytes, White / drug effects
Adipocytes, White / metabolism*
Body Temperature Regulation / genetics
Cold Temperature
Gene Expression Regulation
Glucose / metabolism
Humans
Intra-Abdominal Fat / cytology
Intra-Abdominal Fat / drug effects
Intra-Abdominal Fat / metabolism*
Ion Channels / agonists
Ion Channels / genetics*
Ion Channels / metabolism
Membrane Potential, Mitochondrial / drug effects
Menthol / pharmacology
Mitochondria / drug effects
Mitochondria / metabolism*
Mitochondrial Proteins / agonists
Mitochondrial Proteins / genetics*
Mitochondrial Proteins / metabolism
Primary Cell Culture
Pyrimidinones / pharmacology
Signal Transduction
Subcutaneous Fat / cytology
Subcutaneous Fat / drug effects
Subcutaneous Fat / metabolism*
TRPM Cation Channels / agonists
TRPM Cation Channels / genetics*
TRPM Cation Channels / metabolism
Uncoupling Protein 1

Substances

Ion Channels
Mitochondrial Proteins
Pyrimidinones
TRPM Cation Channels
TRPM8 protein, human
UCP1 protein, human
Uncoupling Protein 1
Menthol
icilin
Glucose