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=Volume 13 - 2022

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=Background: Acute exercise contributes to decreasing 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 the Tubby protein (TUB) can be phosphorylated by JAK2 in CHO-IR cells; we speculate that acute exercise can activate the IL-6/JAK2/TUB pathway to decrease food intake.
Aims: We aim to investigate whether acute exercise induces tyrosine phosphorylation and the association of TUB and JAK2 in the hypothalamus and if IL-6 is involved in this response; furthermore, whether the IL-6/TUB axis is increased by the acute exercise regulates feeding, and if leptin has an additive effect over this mechanism.
Methods: We employed a combination of genetic, pharmacological, and molecular approaches for these purposes.
Key findings: 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: This study suggests a novel hypothalamic pathway by which IL-6 released by exercise regulates feeding.