Interleukin-4 Restores Insulin Sensitivity in Lipid-Induced Insulin-Resistant Adipocytes

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I. S. Stafeev^1,2,a*, S. S. Michurina^1,3, N. V. Podkuychenko^1,3, A. V. Vorotnikov^1,4,b*, M. Yu. Menshikov¹, and Ye. V. Parfyonova^1,2

¹Institute of Experimental Cardiology, National Medical Research Center for Cardiology, 121552 Moscow, Russia

²Lomonosov Moscow State University, Faculty of Basic Medicine, 117192 Moscow, Russia

³Lomonosov Moscow State University, Faculty of Biology, 119991 Moscow, Russia

⁴Lomonosov Moscow State University Medical Center, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received August 29, 2017; Revision received October 26, 2017

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Obesity and latent inflammation in adipose tissue significantly contribute to the development of insulin resistance (IR) and type 2 diabetes. Here we studied whether the antiinflammatory interleukin-4 (IL-4) can restore insulin sensitivity in cultured 3T3-L1 adipocytes. The activity of key components of the insulin signaling cascade was assessed by immunoblotting using phospho-specific antibodies to insulin receptor substrate IRS1 (Tyr612), Akt (Thr308 and Ser473), and AS160 (Ser318) protein that regulates translocation of the GLUT4 glucose transporter to the plasma membrane. IR was induced in mature adipocytes with albumin-conjugated palmitate. IR significantly reduced phosphorylation levels of all the above-mentioned proteins. Addition of IL-4 to the culturing medium during IR induction led to a dose-dependent stimulation of the insulin-promoted phosphorylation of IRS1, Akt, and AS160. At the optimal concentration of 50 ng/ml, IL-4 fully restored activation of the insulin cascade in IR cells, but it did not affect insulin signaling activation in the control cells. IL-4 neither upregulated expression of key adipogenesis markers GLUT4 and PPARγ nor caused lipid accumulation in the adipocytes. These results demonstrate that IL-4 can restore insulin sensitivity in adipocytes via mechanisms not associated with induced adipogenesis or de novo formation of lipid depots.

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KEY WORDS: insulin resistance, interleukin-4, inflammation

DOI: 10.1134/S0006297918050036

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