Cold-sensing TRPM8 channel participates in circadian control of the brown adipose tissue.

Moraes, Maria Nathália; de Assis, Leonardo Vinicius Monteiro; Henriques, Felipe Dos Santos; Batista, Miguel Luiz; Güler, Ali D; Castrucci, Ana Maria de Lauro

Moraes, Maria Nathália; de Assis, Leonardo Vinicius Monteiro; Henriques, Felipe Dos Santos; Batista, Miguel Luiz; Güler, Ali D; Castrucci, Ana Maria de Lauro.

Afiliação

Moraes MN; Institute of Biosciences, Department of Physiology, University of São Paulo, São Paulo, Brazil.
de Assis LVM; Institute of Biosciences, Department of Physiology, University of São Paulo, São Paulo, Brazil.
Henriques FDS; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA; Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
Batista ML; Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
Güler AD; Department of Biology, University of Virginia, Charlottesville, VA, USA.
Castrucci AML; Institute of Biosciences, Department of Physiology, University of São Paulo, São Paulo, Brazil; Department of Biology, University of Virginia, Charlottesville, VA, USA. Electronic address: amdlcast@ib.usp.br.

Biochim Biophys Acta Mol Cell Res ; 1864(12): 2415-2427, 2017 Dec.

Article em En | MEDLINE | ID: mdl-28943398

RESUMO

Transient receptor potential (TRP) channels are known to regulate energy metabolism, and TRPM8 has become an interesting player in this context. Here we demonstrate the role of the cold sensor TRPM8 in the regulation of clock gene and clock controlled genes in brown adipose tissue (BAT). We investigated TrpM8 temporal profile in the eyes, suprachiasmatic nucleus and BAT; only BAT showed temporal variation of TrpM8 transcripts. Eyes from mice lacking TRPM8 lost the temporal profile of Per1 in LD cycle. This alteration in the ocular circadian physiology may explain the delay in the onset of locomotor activity in response to light pulse, as compared to wild type animals (WT). Brown adipocytes from TrpM8 KO mice exhibited a larger multilocularity in comparison to WT or TrpV1 KO mice. In addition, Ucp1 and UCP1 expression was significantly reduced in TrpM8 KO mice in comparison to WT mice. Regarding circadian components, the expression of Per1, Per2, Bmal1, Pparα, and Pparß oscillated in WT mice kept in LD, whereas in the absence of TRPM8 the expression of clock genes was reduced in amplitude and lack temporal oscillation. Thus, our results reveal new roles for TRPM8 channel: it participates in the regulation of clock and clock-controlled genes in the eyes and BAT, and in BAT thermogenesis. Since disruption of the clock machinery has been associated with many metabolic disorders, the pharmacological modulation of TRPM8 channel may become a promising therapeutic target to counterbalance weight gain, through increased thermogenesis, energy expenditure, and clock gene activation.

Assuntos

Tecido Adiposo Marrom/metabolismo; Ritmo Circadiano/genética; Canais de Cátion TRPM/genética; Termogênese/genética; Tecido Adiposo Marrom/crescimento & desenvolvimento; Animais; Metabolismo Energético/genética; Olho/crescimento & desenvolvimento; Olho/metabolismo; Camundongos; Camundongos Knockout; Sensação Térmica/genética

Palavras-chave

Brown adipose tissue; Clock gene machinery; Eye; Mus musculus; Suprachiasmatic nucleus; TRPM8 channel

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tecido Adiposo Marrom / Ritmo Circadiano / Termogênese / Canais de Cátion TRPM Limite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Cell Res Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda

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