title: TRPV1 participates in the activation of clock molecular machinery in the brown adipose tissue in response to light-dark cycle.
abstract: Transient receptor potential (TRPs) channels are involved in thermogenesis, and temperature and energy balance control. Mice lacking TrpV1 become more obese and develop insulin resistance when fed with high fat diet; however, a relationship between metabolic disorders, TRP channels, and clock genes is still unknown. Based on this, we hypothesized that TRPV1 channels would be involved in the synchronization of clock genes in the peripheral tissues. To address this question, we used wild type (WT) and TrpV1 knockout (KO) mice kept in constant darkness (DD) or in light-dark cycle (LD). In WT mouse brown adipose tissue (BAT), TrpV1 oscillated with higher expression at scotophase, Per1 and Per2 showed the same profile, and Bmal1 transcript only oscillated in DD. Interestingly, the oscillatory profile of these clock genes was abolished in TrpV1 KO mice. WT mouse Ucp1 was upregulated in LD as compared to DD, showing no temporal variation; mice lacking TrpV1 showed Ucp1 oscillation with a peak at the photophase. Remarkably, TrpV1 KO mice displayed less total activity than WT only when submitted to LD. We provide evidence that TRPV1 is an important modulator of BAT clock gene oscillations. Therefore, temperature and/or light-dependent regulation of TRPV1 activity might provide novel pharmacological approaches to treat metabolic disorders.
authors.affiliation: Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Maria Nathalia
authors.initials: MN
authors.lastname: Moraes
authors.affiliation: Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Nathana
authors.initials: N
authors.lastname: Mezzalira
authors.affiliation: Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Leonardo Vinicius Monteiro
authors.initials: LV
authors.lastname: de Assis
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Menaker
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Guler
authors.affiliation: Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil. Electronic address: amdlcast@ib.usp.br.
authors.forename: Ana Maria L
authors.initials: AM
authors.lastname: Castrucci
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D003624:Darkness; D020869:Gene Expression Profiling; D008027:Light; D008124:Locomotion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017440:Photoperiod; D050916:TRPV Cation Channels / Q000235:genetics / Q000502:physiology*; D000071256:Uncoupling Protein 1 / Q000235:genetics
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1
keywords: Brown adipose tissue; Clock genes; Locomotor activity; Mus musculus; Temperature; TrpV1; Ucp1