Impaired Local Production of Proresolving Lipid Mediators in Obesity and 17-HDHA as a Potential Treatment for Obesity-Associated Inflammation

Diabetes. 2013 Jun;62(6):1945-56. doi: 10.2337/db12-0828. Epub 2013 Jan 24.

Abstract

Obesity-induced chronic low-grade inflammation originates from adipose tissue and is crucial for obesity-driven metabolic deterioration, including insulin resistance and type 2 diabetes. Chronic inflammation may be a consequence of a failure to actively resolve inflammation and could result from a lack of local specialized proresolving lipid mediators (SPMs), such as resolvins and protectins, which derive from the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We assessed obesity-induced changes of n-3-derived SPMs in adipose tissue and the effects of dietary EPA/DHA thereon. Moreover, we treated obese mice with SPM precursors and investigated the effects on inflammation and metabolic dysregulation. Obesity significantly decreased DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA, resolvin D1 precursor) and protectin D1 (PD1) levels in murine adipose tissue. Dietary EPA/DHA treatment restored endogenous biosynthesis of n-3-derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving insulin sensitivity. Notably, 17-HDHA treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression, and improved glucose tolerance parallel to insulin sensitivity in obese mice. These findings indicate that impaired biosynthesis of certain SPM and SPM precursors, including 17-HDHA and PD1, contributes to adipose tissue inflammation in obesity and suggest 17-HDHA as a novel treatment option for obesity-associated complications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Blotting, Western
  • Docosahexaenoic Acids / metabolism
  • Docosahexaenoic Acids / therapeutic use*
  • Eicosapentaenoic Acid / therapeutic use
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Inflammation / drug therapy*
  • Inflammation / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / drug therapy*
  • Obesity / immunology*
  • Obesity / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • protectin D1
  • Docosahexaenoic Acids
  • 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid
  • Eicosapentaenoic Acid