Hypothalamic IL6/ERK signaling controls lipid oxidation skeletal muscle

Author(s)

Thayana de Oliveira Micheletti

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2015-10-11

Examining board members

Eduardo Rochete Ropelle; Andrey dos Santos; José César Rosa Neto

• Advisor: Eduardo Rochete Ropelle

Abstract

The hypothalamus is a structure of the central nervous system responsible for controlling various organic functions. Recent studies point to an intriguing relationship between the hypothalamus and skeletal muscle metabolism. In this study, we demonstrated that the central action of interleukin 6 (IL6) is able to sensitize the increasing skeletal muscle fatty acid oxidation (FAO) in mice. We identified that this action occurs through the activation of the ERK 1/2 hypothalamic, since the infused intracerebroventricularly (ICV) of the pharmacological inhibitor of ERK1 / 2, PD98059, abolished the effect of IL6 central FAO in skeletal muscle. To evaluate the physiological relevance of these findings, we observed that exercise was able to stimulate via IL6 / ERK1 / 2 in the ventromedial hypothalamus (VMH) and activate the FAO in skeletal muscle. On the other hand central inhibition action of IL6 through ICV injection of anti-IL-6 antibody in mice attenuated the effect of exercise on muscle FAO. Additionally, IL6 knockout mice (IL6KO) showed deficiency in OAG in muscle when subjected to exercise. Whereas exogenous infusion of recombinant IL6 ICV restored the effect on activation of muscle FAO in IL6KO animals. Finally, we identified that the communication between the hypothalamus and skeletal muscle occurs through ?2AC adrenergic pathway, since the use of the inhibitor of this pathway, yohimbine, abolished FAO activation promoted by ICV injection of recombinant IL6, the same response observed in mice double knockout ?2AC adrenergic receptors. Collectively, these results show that the pathway IL6 / ERK1 / 2 hypothalamic participates in the FAO muscle in mice (AU)

• FAPESP's process: 12/23006-1 - Effect of IL-6 on the hypothalamic activation of AMPK / ACC in skeletal muscle of mice: The role of physical exercise.
• Grantee: Thayana de Oliveira Micheletti
• Support Opportunities: Scholarships in Brazil - Master