Kinin B1 receptor modulates mitochondrial activity responsivity in fasting and voluntary exercise

Autor(es)

Arruda, Adriano Cleis ; Budu, Alexandre ; de Menezes, Thiago Nunes ; Bader, Michael ; Araujo, Ronaldo Carvalho ; Freitas-Lima, Leandro Ceotto

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 309, p. 9-pg., 2022-10-07.

Resumo

The Kallikrein-Kinin System (KKS) plays an important role in energy metabolism. We have previously described the importance of the kinin B1 receptor (B1R) in metabolism regulation. Considering that the liver manages the different energy demands of different body tissues, we combined two stressful conditions - fasting and voluntary exercise - to address how B1R may affect liver metabolism, focusing on mitochondrial function.Aims: To investigate how the kinin B1 receptor (B1R) modulates mitochondrial activity under stress conditions, focusing on the rate of energy expenditure and shift in metabolism. Main methods: Wild-type and B1R-knockout (B1KO) male mice remained in a calorimetric cage with a wheel for 7 days; 48 h before euthanasia, half of the animals from both groups were submitted to fasting conditions. Mitochondrial activity, ketone bodies, and gene expression involving mitochondrial activity were evaluated.Key findings: B1R modulates the mitochondrial activity under fasting and voluntary exercise, reducing the VO2 expenditure and HEAT. B1KO animals who exercised and underwent fasting did not have increased glucose levels, suggesting a preference for lipids as an energy source. Moreover, these animals displayed RER around 0.8, which indicates a beta-oxidation increment. Interestingly, the lack of B1R did not induce mitochondrial activity and biogenesis, suggesting interference in metabolism responsivity, a condition modulated by sirtuins under PGC-1 alpha control.Significance: B1R modulates mitochondrial respiratory control ratios, which suggests metabolic suppression, influencing hepatic metabolism and, consequently, energy homeostasis. (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: 15/20082-7 - Sistema calicreína cininas no exercício físico e metabolismo
• Beneficiário: Ronaldo de Carvalho Araújo
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/23599-6 - Receptores de cininas e imunometabolismo
• Beneficiário: Leandro Ceotto Freitas Lima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado