Muscle Function and Homeostasis Require Cytokine Inhibition of AKT Activity in

Overview

Journal Elife

Specialty Biology

Date 2020 Jan 17

PMID 31944178

Citations 13

Authors

Katrin Kierdorf

Fabian Hersperger

Jessica Sharrock

Crystal M Vincent

Pinar Ustaoglu

Jiawen Dou

Attila Gyoergy

Olaf Gross

Daria E Siekhaus

Marc S Dionne

Affiliations

Soon will be listed here.

Abstract

ligands are secreted signals that act via a GP130-like receptor, , to activate JAK/STAT signalling in . Like many mammalian cytokines, can be activated by infection and other stresses and can promote insulin resistance in target tissues. However, the importance of this effect in non-inflammatory physiology is unknown. Here, we identify a requirement for -JAK signalling as a metabolic regulator in healthy adult muscle. Adult muscles show basal JAK-STAT signalling activity in the absence of any immune challenge. Plasmatocytes ( macrophages) are an important source of this tonic signal. Loss of the receptor on adult muscles significantly reduces lifespan and causes local and systemic metabolic pathology. These pathologies result from hyperactivation of AKT and consequent deregulation of metabolism. Thus, we identify a cytokine signal that must be received in muscle to control AKT activity and metabolic homeostasis.

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