Metabolic fasting stress is ameliorated in Kinin B1 receptor-deficient mice

Autor(es)

Freitas-Lima, Leandro Ceotto ; Budu, Alexandre ; Estrela, Gabriel Rufino ; Alves-Silva, Thais ; Perilhao, Mauro Sergio ; Arruda, Adriano Cleis ; Araujo, Ronaldo Carvalho

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 294, p. 9-pg., 2022-02-16.

Resumo

The liver has an essential role in responding to metabolic demands under stress conditions. The organ stores, releases, and recycles metabolism-related substrates. However, it is not clear how the Kallikrein-Kinin System modulates metabolic flexibility shift between energetic sources.Aims: To analyze the hepatic metabolism in kinin B1 receptor deficient mice (B1KO mice) under fasting conditions.Main methods: WT and B1KO male mice were allocated in a calorimetric cage for 7 days and 48 h before the euthanasia, half of the animals of both groups were under fasting conditions. Biochemical parameters, ketone bodies (KB), and gene expression involving the liver energetic metabolism genes were evaluated.Key findings: Kinin B1 receptor (B1R) modulates the metabolic shift under fasting conditions, reducing the VO2 expenditure. A preference for carbohydrates as an energetic source is suggested, as the B1KO group did not display an increase in KB in the serum. Moreover, the B1KO animals displayed higher serum triglycerides concentration compared to WT fasting mice. Interestingly, the lack of B1R induces the increase expression of enzymes from the glycolysis and lipolysis pathways under the fed. However, under fasting, the enzymatic expression of gluconeogenesis, glyceroneogenesis, and ketogenesis of these pathways does not occur, suggesting an absence of the shift metabolism responsivity, and this condition is modulated by PDK4 under FOXO1 control.Significance: B1R has an important role in the hepatic glucose metabolism, which in turn influences the energetic metabolism, and in long-term outcomes, such as in the decrease in hepatic glycogen stores and in the enhancement of hepatic metabolism. (AU)

• Processo FAPESP: 13/06207-6 - Papel do exercício físico e da restrição calórica na lesão renal aguda induzida pela cisplatina
• Beneficiário: Gabriel Rufino Estrela
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/23599-6 - Receptores de cininas e imunometabolismo
• Beneficiário: Leandro Ceotto Freitas Lima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/20082-7 - Sistema calicreína cininas no exercício físico e metabolismo
• Beneficiário: Ronaldo de Carvalho Araújo
• Modalidade de apoio: Auxílio à Pesquisa - Temático