Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in ob/ob and diet-induced obese mice

FASEB J. 2017 May;31(5):2135-2145. doi: 10.1096/fj.201600859R. Epub 2017 Feb 10.

Abstract

The beneficial actions of n-3 fatty acids on obesity-induced insulin resistance and inflammation have been related to the synthesis of specialized proresolving lipid mediators (SPMs) like resolvins. The aim of this study was to evaluate the ability of one of these SPMs, maresin 1 (MaR1), to reverse adipose tissue inflammation and/or insulin resistance in two models of obesity: diet-induced obese (DIO) mice and genetic (ob/ob) obese mice. In DIO mice, MaR1 (2 μg/kg; 10 d) reduced F4/80-positive cells and expression of the proinflammatory M1 macrophage phenotype marker Cd11c in white adipose tissue (WAT). Moreover, MaR1 decreased Mcp-1, Tnf-α, and Il-1β expression, upregulated adiponectin and Glut-4, and increased Akt phosphorylation in WAT. MaR1 administration (2 μg/kg; 20 d) to ob/ob mice did not modify macrophage recruitment but increased the M2 macrophage markers Cd163 and Il-10. MaR1 reduced Mcp-1, Tnf-α, Il-1β, and Dpp-4 and increased adiponectin gene expression in WAT. MaR1 treatment also improved the insulin tolerance test of ob/ob mice and increased Akt and AMPK phosphorylation in WAT. These data suggest that treatment with MaR1 can counteract the dysfunctional inflamed WAT and could be useful to improve insulin sensitivity in murine models of obesity.-Martínez-Fernández, L., González-Muniesa, P., Laiglesia, L. M., Sáinz, N., Prieto-Hontoria, P. L., Escoté, X., Odriozola, L., Corrales, F. J., Arbones-Mainar, J. M., Martínez, J. A., Moreno-Aliaga, M. J. Maresin 1 improves insulin sensitivity and attenuates adipose tissue inflammation in ob/ob and diet-induced obese mice.

Keywords: DHA; adipokines; glucose metabolism; macrophages; n-3 PUFAs derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Adipose Tissue, White / metabolism
  • Animal Feed
  • Animals
  • Diet*
  • Docosahexaenoic Acids / pharmacology*
  • Inflammation / metabolism*
  • Insulin Resistance / physiology*
  • Interleukin-10 / metabolism
  • Macrophages / metabolism
  • Male
  • Mice, Inbred C57BL
  • Obesity / metabolism*

Substances

  • 7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid
  • IL10 protein, mouse
  • Interleukin-10
  • Docosahexaenoic Acids