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

• Published in: International journal of molecular sciences 2022-06, Vol.23 (13), p.7014
• Main Authors: Lacerda, José Thalles, Gomes, Patrícia R. L., Zanetti, Giovanna, Mezzalira, Nathana, Lima, Otoniel G., de Assis, Leonardo V. M., Guler, Ali, Castrucci, Ana Maria, Moraes, Maria Nathália
• Format: Article
• Language: English
• Subjects: AKT protein; Body fat; Capsaicin receptors; Circadian rhythm; Clock systems; Energy; Enzymes; Gene expression; Genotype & phenotype; Glucagon; Gluconeogenesis; Glucose; Glucose metabolism; Glucose transporter; Glycogen; Glycogens; Homeostasis; Inflammation; Kinases; Lipid metabolism; Lipids; Liver; Metabolism; Period 1 protein; Peroxisome proliferator-activated receptors; Physiology; Protein kinase A; Proteomes; Proteomics; Rodents; Signal transduction; Transient receptor potential proteins
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23137014

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 Pparα, Pparγ, 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.