RT Journal Article
SR Electronic
T1 Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 157529
DO 10.1101/157529
A1 Elena Tarabra
A1 Ting-Wen An Lee
A1 Victor A Zammit
A1 Manu Vatish
A1 Eijiro Yamada
A1 Jeffrey E Pessin
A1 Claire C Bastie
YR 2017
UL http://biorxiv.org/content/early/2017/06/29/157529.abstract
AB Diet-induced obesity is associated with increased adipose tissue activated macrophage numbers. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency (FynKO) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in FynKO bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. Saturated palmitate activates Fyn and re-localizes Fyn into the nucleus of RAW264.7, J774 and wild-type bone marrow-derived macrophages. Similarly, Fyn activity is increased in cells of AT stromal vascular fraction of high fat-fed control mice, with Fyn protein being located in the nucleus of these cells. We demonstrate that Fyn modulates palmitate-dependent oxidative stress in macrophages. Moreover, Fyn catalytic activity is necessary for its nuclear re-localization and downstream effects, as Fyn pharmacological inhibition abolishes palmitate-induced Fyn nuclear redistribution and palmitate-dependent increase of oxidative stress markers. Importantly, mono-or polyunsaturated FAs do not activate Fyn, and fail to re-localize Fyn to the nucleus. Together these data demonstrate that macrophages integrate nutritional FA signals via a differential activation of Fyn that distinguishes, at least partly, the effects of saturated versus unsaturated fats.ABBREVIATIONSKOKnockoutWTWild TypeBMDMBone Marrow Derived MacrophagesHFDhigh fat dietNrf2Nuclear-factor erythroid2-related factor2AMPKAMP-activated protein kinaseDHAdocosahexaenoic acidPApalmitateSVFstromal vascular fractionROSreactive oxygen species