TRPV1 inactivation alters core body temperature and serum corticosterone levels: Impacts on clock genes expression in the liver and adrenal glands

Nayara Ac Horta; Paola Fernandes; Thais Sr Cardoso; Frederico Sm Machado; Lucas R Drummond; Cândido C Coimbra; Samuel P Wanner; Ana Maria L Castrucci; Maristela O Poletini

doi:10.1016/j.jtherbio.2023.103514

TRPV1 inactivation alters core body temperature and serum corticosterone levels: Impacts on clock genes expression in the liver and adrenal glands

J Therm Biol. 2023 May:114:103514. doi: 10.1016/j.jtherbio.2023.103514. Epub 2023 Feb 14.

Authors

Nayara Ac Horta¹, Paola Fernandes¹, Thais Sr Cardoso¹, Frederico Sm Machado¹, Lucas R Drummond¹, Cândido C Coimbra¹, Samuel P Wanner², Ana Maria L Castrucci³, Maristela O Poletini⁴

Affiliations

¹ Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
² Exercise Physiology Laboratory, School of Physical Education, Physical Therapy and Occupational Therapy, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
³ Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil.
⁴ Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: marispoletini@icb.ufmg.br.

PMID: 37344011
DOI: 10.1016/j.jtherbio.2023.103514

Abstract

Purpose: TRPV1 desensitization or blockade promotes hyperthermia in rodents. Daily changes in core body temperature (Tc), spontaneous locomotor activity (SLA), and glucocorticoids are temporal cues for peripheral clocks. Thus, this study aimed to evaluate the effects of both desensitization and blockade of TRPV1 on Tc, SLA, blood corticosterone, and the clock genes Per1 and Bmal1 in the liver and adrenal.

Methods and results: Resiniferatoxin (RTX, 20 μg kg^-1) known to desensitize the intra-abdominal TRPV1 channels was i. p. administered in adult male rats. One day after, RTX rats displayed higher Tc than vehicle rats (control) in the light and dark phases. RTX rats showed higher corticosterone at zeitgeber time (ZT) 6 and ZT12 compared to ZT0. Control rats showed a rise in corticosterone at ZT12. RTX abolished the Per1 peak in both the liver and adrenal glands, whereas it enhanced the peak of Bmal1 expression in the liver and decreased it in adrenal glands. Circadian variation in Tc and SLA was unaffected despite higher Tc being found along the light phase up to 5 days after RTX injection. Acute blockade of TRPV1 with the antagonist AMG-517 injected at ZT0 increased Tc and reduced corticosterone without affecting SLA. In the liver, while AMG-517 did not affect Per1, it increased Bmal1 mRNA. In adrenal glands, AMG-517 increased Per1 and did not affect Bmal1 expression. Although rats exposed to a 60-min 34 °C environment showed similar hyperthermia to that observed in AMG-517 rats, neither corticosterone nor liver nor adrenal clock genes changed.

Conclusions: Inactivation of TRPV1 by abdominal desensitization or by antagonism alters the time-of-day changes of clock genes expression in the liver and adrenal, as well as corticosterone. TRPV1 may be necessary for signaling cyclical temporal cues for clock genes in the periphery but less critical for the circadian profile of Tc and SLA.

Keywords: Circadian rhythm; Desensitization; Hyperthermia; Peripheral clocks; Suprachiasmatic nucleus; Temperature.

MeSH terms

ARNTL Transcription Factors* / genetics
ARNTL Transcription Factors* / metabolism
Adrenal Glands / metabolism
Animals
Body Temperature
Circadian Rhythm / physiology
Corticosterone*
Liver / metabolism
Male
Rats

Substances

ARNTL Transcription Factors
Corticosterone
Trpv1 protein, rat