title: Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production.
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.
authors.affiliation: Department of Medicine - DIMED, Clinica Medica 3, School of Medicine, University of Padova, Padova, Italy. Electronic address: marco.rossato@unipd.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Rossato
authors.affiliation: Department of Medicine - DIMED, Clinica Medica 3, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Marnie
authors.initials: M
authors.lastname: Granzotto
authors.affiliation: Department of Molecular Medicine, Section of Anatomy, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Macchi
authors.affiliation: Department of Molecular Medicine, Section of Anatomy, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Porzionato
authors.affiliation: Department of Molecular Medicine, Section of Anatomy, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Petrelli
authors.affiliation: Department of Medicine - DIMED, Clinica Medica 3, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Calcagno
authors.affiliation: Department of Animal Medicine, Production and Health, University of Padova, Padova, Italy.
authors.forename: Juri
authors.initials: J
authors.lastname: Vencato
authors.affiliation: Department of Biomedical Sciences, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: De Stefani
authors.affiliation: Department of Medicine - DIMED, Clinica Medica 3, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Silvestrin
authors.affiliation: Department of Biomedical Sciences, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
authors.affiliation: Department of Neurosciences, Plastic Surgery Clinic, University of Padova, Padova, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Bassetto
authors.affiliation: Department of Molecular Medicine, Section of Anatomy, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caro
authors.affiliation: Department of Medicine - DIMED, Clinica Medica 3, School of Medicine, University of Padova, Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
mesh_terms: D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001833:Body Temperature Regulation / Q000235:genetics; D003080:Cold Temperature; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008610:Menthol / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D011744:Pyrimidinones / Q000494:pharmacology; D015398:Signal Transduction; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D011744:Pyrimidinones; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D008610:Menthol; C490483:icilin; D005947:Glucose
keywords: Human adipocyte; Menthol; Mitochondria; TRPM8; UCP1