Acute exercise reduces feeding by activating IL-6/Tubby axis in the mouse hypothalamus

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Micheletti, Thayana de Oliveira ; dos Santos, Andressa Cassia ; Rocha, Guilherme Zweig ; Silva, Vagner Ramon Rodrigues ; Quaresma, Paula Gabriele Fernandes ; Assalin, Heloisa Balan ; Junqueira, Felipe Silva ; Ropelle, Eduardo Rochete ; Oliveira, Alexandre Gabarra ; Saad, Mario Jose Abdalla ; Prada, Patricia de Oliveira

• Document type: Journal article
• Source: FRONTIERS IN PHYSIOLOGY; v. 13, p. 16-pg., 2022-11-14.

Abstract

Background: Acute exercise contributes to decreased feeding through leptin and interleukin/Janus kinase 2/signal transducers and activators of transcription 3 (IL-6/JAK2/STAT3) signaling. Considering the pleiotropic use of substrates by JAK2 and that JAK2 can phosphorylate the Tubby protein (TUB) in CHO-IR cells, we speculated that acute exercise can activate the IL-6/JAK2/TUB pathway to decrease food intake.Aims: We investigated whether acute exercise induced tyrosine phosphorylation and the association of TUB and JAK2 in the hypothalamus and if IL-6 is involved in this response, whether acute exercise increases the IL-6/TUB axis to regulate feeding, and if leptin has an additive effect over this mechanism.Methods: We applied a combination of genetic, pharmacological, and molecular approaches.Key findings: The in vivo experiments showed that acute exercise increased the tyrosine phosphorylation and association of JAK2/TUB in the hypothalamus, which reduced feeding. This response was dependent on IL-6. Leptin had no additive effect on this mechanism.Significance: The results of this study suggest a novel hypothalamic pathway by which IL-6 released by exercise regulates feeding and reinforces the beneficial effects of exercise. (AU)

• FAPESP's process: 09/08075-4 - Hypothalamic nuclei regulation of tub: the effects of leptin, insulin, fasting, aging and high fat feeding
• Grantee: Patrícia de Oliveira Prada
• Support Opportunities: Scholarships in Brazil - Young Researchers