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

Author(s)

Moraes, Maria Nathalia ^[1] ; Monteiro de Assis, Leonardo Vinicius ^[1] ; Henriques, Felipe dos Santos ^{[2, 3]} ; Batista, Jr., Miguel Luiz ^[2] ; Guler, Ali D. ^[4] ; de Lauro Castrucci, Ana Maria ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Dept Physiol, Inst Biosci, Sao Paulo - Brazil

^[2] Univ Mogi das Cruzes, Integrated Grp Biotechnol, Lab Adipose Tissue Biol, Mogi Das Cruzes - Brazil

^[3] Univ Massachusetts, Med Sch, Program Mol Med, Worcester, MA 01605 - USA

^[4] Univ Virginia, Dept Biol, Charlottesville, VA - USA

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH; v. 1864, n. 12, p. 2415-2427, DEC 2017.
• Web of Science Citations: 7

Abstract

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 Peri 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 TrpVl KO mice. In addition, Ucpl and UCP1 expression was significantly reduced in TrpM8 KO mice in comparison to WT mice. Regarding circadian components, the expression of Perl, Per2, Bmall, Ppar alpha, and Pparjl 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. (AU)

• FAPESP's process: 12/50214-4 - Biological clock setting by light and temperature: phylogenetic aspects
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Research Projects - Thematic Grants