AUTHOR=de Oliveira Micheletti Thayana , Cassia dos Santos Andressa , 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 

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

JOURNAL=Frontiers in Physiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.956116

DOI=10.3389/fphys.2022.956116

ISSN=1664-042X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Aims:</bold> 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.</p><p><bold>Methods:</bold> We applied a combination of genetic, pharmacological, and molecular approaches.</p><p><bold>Key findings:</bold> The <italic>in vivo</italic> 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.</p><p><bold>Significance:</bold> 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.</p>