The role of physical exercise and omega-3 fatty acids in the modulation of GPR120 expression in the liver of obese animals: the impact in the control of glucose homeostasis

Author(s)

Guilherme Pedron Formigari

• Document type: Master's Dissertation
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2016-03-29

Examining board members

Dennys Esper Cintra; Eduardo Rochete Ropelle; Ronaldo Vagner Thomatiele dos Santos

• Advisor: Dennys Esper Cintra

Abstract

Introduction: Obesity is a condition out of control, wherein antiinflammatory therapies or surgical procedures are ineffective. A low grade and chronic inflammation is considered the main characteristic of obesity and contributes to the metabolic derangement. In this context, the liver appears as one of the affected organs. In general, omega-3 fatty acids can help reduce the inflammation through its receptor, GPR120, which interrupt the inflammatory process originated from Toll and cytokines receptors. However, the mechanisms responsible for regulating GPR120 expression are still not completely understood. In parallel, physical exercise is also able to reduce the progression of the inflammatory signal. However, little is known about the role of physical exercise on the modulation of GPR120 expression. Objectives: The aim of this study was to evaluate the modulation of expression of unsaturated fatty acid receptor, GPR120, in the liver of lean and obese mice after sessions of acute and chronic aerobic exercise. Moreover, we evaluate if the omega-3 supplementation together or not with chronic physical exercise could affect GPR120 expression. Furthermore, the metabolic repercussions in the liver and the pathways of glycogen, gluconeogenesis and inflammation were evaluated. Materials and Methods: Swiss mice at 4 weeks-age were subjected to an acute aerobic exercise session, wherein fragments of the hepatic tissue were extracted at different times for analysis of gene expression and protein content of GPR120. In parallel, a group of mice was fed on a standard chow (CT) and another group was fed on a high fat diet for 8 weeks. After this period, obese mice were divided in four groups: sedentary obese (OB), trained obese (OB+EXE), obese + flax seed oil (OB+OL) ? 100 µL of flax seed oil for 30 days; trained obese + flax seed oil (OB+EXE+OL). Gas chromatography were performed to analyze the constitution of flax seed oil. The pathways of insulin, inflammation, glycogen and omega-3 were assessed by immunobloting. The insulin sensitivity was evaluated by intraperitoneal insulin tolerance test and glycogen content was analyzed by spectrophotometry. Analysis of variance followed Tukey¿s test were used and P<0.05 was accepted as statistically significant. Results: The acute aerobic exercise was not able to increase gene expression and protein content of GPR120. Nevertheless, the chronic aerobic exercise increased protein content of GPR120 in the liver of obese mice compared with sedentary obese group (P<0,05). In addition, flax seed oil treatment was also able to increase protein content of GPR120 (P<0,05). Moreover, chronic physical exercise together or not with flax seed oil increased insulin sensitivity (P<0,05). Furthermore, chronic exercise and flax seed oil supplementation were able to reduce activity and content of inflammatory markers (P<0,05). However, physical exercise and flax seed oil did not increase glycogen content compared with OB group. Conclusion: The nutrigenomics and fisiogenomics strategies employed in this project showed that chronic aerobic exercise and flax seed oil suplemmentation were able to increase protein content of GPR120 in the liver of obese mice. In addition, these approaches decreased the progression of inflammatory signaling. Furthermore, we did not see a synergistic effect between physical exercise and flax seed oil. However, both contributed significantly to restoration of hepatic signaling (AU)

• FAPESP's process: 14/15258-6 - Modulation of hepatic expression of GPR120 receptor mediated physical exercise in obese rodents
• Grantee: Guilherme Pedron Formigari
• Support Opportunities: Scholarships in Brazil - Master