Cold challenge and its effects on thermosensor canonical processes in BAT and their possible interaction with TRP channels

Author(s)

Otoniel Gonçalves de Lima

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2021-05-17

Examining board members

Ana Maria de Lauro Castrucci; Patricia Rodrigues Lourenço Gomes; Regina Pekelmann Markus; Patrícia Reckziegel

• Advisor: Ana Maria de Lauro Castrucci

Abstract

The daily environmental temperature oscillations promote strong changes in metabolism and thermogenic activity of the brown adipose tissue in mammals. The natriuretic peptides (NPs) and their receptors (NP-A, NP-B and NP-C) modulate thermogenic activity through the induction of Ucp1 expression and other genes related to lipid and mitochondrial metabolism in BAT. Aiming to explore the role of TRPA1 channel in cold-evoked responses, we investigated, in WT C57Bl/ 6J and knockout Trpa1 (KO) mice, the effect of 22oC exposure on the expression. of the clock genes Per1 e Bmal1, the receptor genes Npra, Nprb and Nprc, the blood levels of ANP and BNP, as well as the genes involved in the thermogenic activity and lipid metabolism (Ucp1, Pgc1?, Prdm16, Lcad, Cidea, Cpt1α) in both genotypes\' BAT. Initially, we determine the thermoneutrality range and the body weight after two and four weeks. 30oC is within the neutral temperature range and, therefore, we used it as the control for both genotypes. As to body weight, it did not change under any of the experimental conditions, except for the Trpa1 KO animals submitted to 22oC, which gained less weight as compared to the same genotype at 30°C or to WT at 22°C. As expected, the clock genes Per1 e Bmal1 oscillated in antiphase, peaking in the dark and light phase, respectively in the thermoneutral temperature. The lack of the TRPA1 channel seems not to affect this pattern; however, Trpa1 KO mice had a reduction in Per1 mRNA after exposure to 22°C for two weeks. Our results demonstrated that in the animals subject to 22oC for 2 weeks, there was a decrease of transcripts of all three subtypes of NP receptors and, curiously, Nprc expression. increased after 4 weeks at 30oC. Furthermore, BNP plasma levels at 22oC remained unaffected in Trpa1 knockout animals, or even diminished in WT, in comparison with 30oC. These concentrations increased in both genotypes only after an acute 10oC challenge. Raising the question whether the stimulus extreme or its duration triggers the NP pathway. As to the thermogenic pathway genes, just Ucp1 and Lcad transcripts increased in both genotypes, whereas several components of the pathway, Prdm16, Cidea, Cpt1, were remarkably increased in the Trpa1 channel knockouts. (AU)

• FAPESP's process: 18/23915-8 - Cold challenge and its effects on canonical thermosensation processes in BAT and their possible interaction with TRP channels
• Grantee: Otoniel Gonçalves de Lima
• Support Opportunities: Scholarships in Brazil - Master