Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages

• Published in: Oncotarget Vol. 8; no. 49; pp. 86634 - 86645
• Main Authors: Tarabra, Elena, An Lee, Ting-Wen, Zammit, Victor A, Vatish, Manu, Yamada, Eijiro, Pessin, Jeffrey E, Bastie, Claire C
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 17.10.2017
• Subjects: Research Paper; adipose tissue; macrophages; fatty acids; obesity; Fyn kinase
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.21258

Diet-induced obesity is associated with increased adipose tissue activated macrophages. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency ( ) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. 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 adipose tissue 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.