TY - JOUR
T1 - TRPV1 participates in the activation of clock molecular machinery in the brown adipose tissue in response to light-dark cycle
AU - Moraes, Maria Nathalia
AU - Mezzalira, Nathana
AU - de Assis, Leonardo Vinicius Monteiro
AU - Menaker, Michael
AU - Guler, Ali
AU - Castrucci, Ana Maria L.
N1 - Funding Information:
This work was partially supported by the Sao Paulo Research Foundation (FAPESP, grant 2012/50214-4 ) and by the National Council of Technological and Scientific Development (CNPq, grant 301293/2011-2 and 303070/2015-3 ), Brazil. MN Moraes, N Mezzalira and LVM de Assis are fellows of FAPESP (2014/16412-9, 2013/02131-5, 2013/24337-4 respectively). We are thankful to Aundrea Rainwater (University of Virginia, USA) for technical support. The authors declare no competing financial interests.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84999053637&partnerID=8YFLogxK
U2 - 10.1016/j.bbamcr.2016.11.010
DO - 10.1016/j.bbamcr.2016.11.010
M3 - Journal articles
C2 - 27864077
AN - SCOPUS:84999053637
SN - 0167-4889
VL - 1864
SP - 324
EP - 335
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
IS - 2
ER -