TRPV1 participates in the activation of clock molecular machinery in the brown adipose tissue in response to light-dark cycle

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...

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Veröffentlicht in:Biochimica et biophysica acta. Molecular cell research 2017-02, Vol.1864 (2), p.324-335
Hauptverfasser: Moraes, Maria Nathalia, Mezzalira, Nathana, de Assis, Leonardo Vinicius Monteiro, Menaker, Michael, Guler, Ali, Castrucci, Ana Maria L.
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •TrpV1 KO mice exhibited a reduction of locomotor activity as compared to WT mice.•The oscillation of Per1, Per2 and Bmal1 in WT BAT was abolished in TrpV1 KO mice.•WT mouse Ucp1 was upregulated in LD as compared to DD.•In TrpV1 KO mice there was a shift of the photophase peak of Ucp1 transcript.•TrpV1 KO mice showed reduced Rev-erbα expression in the scotophase.
ISSN:0167-4889
1879-2596
DOI:10.1016/j.bbamcr.2016.11.010