Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes

Author(s)

Lacerda, Jose Thalles ; Gomes, Patricia R. L. ; Zanetti, Giovanna ; Mezzalira, Nathana ; Lima, Otoniel G. ; de Assis, Leonardo V. M. ; Guler, Ali ; Castrucci, Ana Maria ; Moraes, Maria Nathalia

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 13, p. 24-pg., 2022-07-01.

Abstract

To investigate the role of the transient receptor potential channel vanilloid type 1 (TRPV1) in hepatic glucose metabolism, we analyzed genes related to the clock system and glucose/lipid metabolism and performed glycogen measurements at ZT8 and ZT20 in the liver of C57Bl/6J (WT) and Trpv1 KO mice. To identify molecular clues associated with metabolic changes, we performed proteomics analysis at ZT8. Liver from Trpv1 KO mice exhibited reduced Per1 expression and increased Ppar alpha, Ppar gamma, Glut2, G6pc1 (G6pase), Pck1 (Pepck), Akt, and Gsk3b expression at ZT8. Liver from Trpv1 KO mice also showed reduced glycogen storage at ZT8 but not at ZT20 and significant proteomics changes consistent with enhanced glycogenolysis, as well as increased gluconeogenesis and inflammatory features. The network propagation approach evidenced that the TRPV1 channel is an intrinsic component of the glucagon signaling pathway, and its loss seems to be associated with increased gluconeogenesis through PKA signaling. In this sense, the differentially identified kinases and phosphatases in WT and Trpv1 KO liver proteomes show that the PP2A phosphatase complex and PKA may be major players in glycogenolysis in Trpv1 KO mice. (AU)

• FAPESP's process: 17/24615-5 - Breaking a paradigm? Melanopsin, a canonical photo-pigment, acting as sensor to entrain the clock in light unexposed organs, and its putative interaction with TRP channels: a trans-disciplinary study involving physiological and pathological aspects
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/01659-2 - Participation of melanopsin in the thermoregulation of mammals
• Grantee: Giovanna Zanetti
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/16412-9 - Mechanisms of clock genes thermo-modulation in peripheral tissue of mammals: role of TRP channels
• Grantee: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/04524-8 - Integrating proteogenomics approach and system biology to investigate the role of melanopsin and TRP channels in the circadian rhythmicity
• Grantee: José Thalles Jocelino Gomes de Lacerda
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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
• FAPESP's process: 18/16511-8 - Involvement of the photosensitive and temporal controlling systems in the development, progression, and metastasis of malignant melanoma: an investigation of novel therapeutic targets
• Grantee: Leonardo Vinícius Monteiro de Assis
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/02131-5 - Effects of light and temperature on clock genes expression in amphibians and mammals: the pigment cell as a study model
• Grantee: Nathana Fernandes Mezzalira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/50214-4 - Biological clock setting by light and temperature: phylogenetic aspects
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/14728-0 - Melanopsin as the UVA photoreceptor and its relationship with pigmentation, DNA repair, biological clock and components of the HPA axis: a novel pharmacological target?
• Grantee: Ana Maria de Lauro Castrucci
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/26651-9 - Glaucoma as a model of temporal information disruption: impact on the metabolism
• Grantee: Maria Nathália de Carvalho Magalhães Moraes Figueira Borges
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 21/09923-0 - The role of melatonin on the heritable variation in the endocrine pancreas of the offspring of rats in hypomelatoninemia during pregnancy: From B cell transdifferentiation to epigenetics.
• Grantee: Patrícia Rodrigues Lourenço Gomes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral