Effects of different physical training protocols in biomolecular pathways of hepatic glucose production control and lipid metabolism in the liver of obese rodents

Author(s)

Rodrigo Martins Pereira

• Document type: Doctoral Thesis
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2021-12-20

Examining board members

Leandro Pereira de Moura; Rodrigo Augusto Dalia; Paulo Henrique Canciglieri; Carlos Kiyoshi Katashima; Célio Junior da Costa Fernandes

• Advisor: Leandro Pereira de Moura

Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive liver fat accumulation and is closely related to obesity and type 2 diabetes mellitus (T2DM). The liver is one of the main organs responsible for normoglycemia, and the fight against NAFLD to increase hepatic insulin action is one of the main strategies in T2DM management. Despite medical advances, the plysical training is the primary interventions for increasing the hepatic insulin sensivity and reducing NAFLD in obese individuals. However, the mechanisms involved in these processes are not fully understood. The our aim was to investigate biomolecular mechanisms by which different physical training protocols act against NAFLD and increase insulin sensivity and hepatic glucose production (HGP) control in obese mice. After Ethics Committee approval, male Swiss mice were fed a high saturated fat diet for obesity induction and then subjected to different training protocols: ladder climb strength training, treadmill aerobic training and combined training (strength and aerobic in the same session). Strength training consisted of 1 daily session for 15 days; aerobic training in 1 daily session for 7 days; and the combined training in 1 daily session for 7 days. Strength training reduced NAFLD, inhibiting the activity of the lipogenic protein Acetyl-CoA carboxylase (ACC), reducing the protein content of Fatty Acid Synthase (FAS) and ACC and the messenger RNA levels of Fasn and Scd1. We also observed a reduction in Forkhead box protein O1 (FOXO1) activity, reducing Glucose 6 Phosphatase (G6Pase) and Phosphoenolpyruvate Carboxykinase (PEPCK). The gluconeogenic protein levels of Pyruvate Carboxylase (PC) and inflammation-induced protein Protein tyrosine phosphatase 1B (PTP1B) were also reduced. When we analyzed combined training, we found that this modality also reduced NAFLD and lipogenic stimulation. Finally, we observed that both strength and aerobic training increased clusterin hepatic content in obese animals. Together, these results allow us to conclude that the 3 exercise training protocols have interesting potential against NAFLD, reducing liver lipids, inhibiting the hepatic lipogenesis machinery and improving the control of HGP (AU)

• FAPESP's process: 16/12569-6 - Effects of different exercise intensities on clusterin metabolism and its interference on insulin signaling in rodents
• Grantee: Rodrigo Martins Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)