Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty acids

Diabetologia. 2006 Sep;49(9):2109-19. doi: 10.1007/s00125-006-0300-x. Epub 2006 Jun 17.


Aims/hypothesis: Inflammatory alterations in white adipose tissue appear to underlie complications of obesity including diabetes mellitus. Polyunsaturated fatty acids (PUFA), particularly those of the n-3 series, modulate immune responses and may ameliorate insulin sensitivity. In this study, we investigated how PUFA affect white adipose tissue inflammation and gene expression in obese diabetic animals.

Materials and methods: We treated db/db mice as well as lean non-diabetic mice (db/+) with either low-fat standard diet (LF) or high-fat diets rich in (1) saturated/monounsaturated fatty acids (HF/S), (2) n-6 PUFA (HF/6) and (3) the latter including purified marine n-3 PUFA (HF/3).

Results: Many genes involved in inflammatory alterations were upregulated in db/db mice on HF/S compared with LF in parallel with phosphorylation of c-Jun N-terminal kinase (JNK). In parallel, adipose tissue infiltration with macrophages was markedly enhanced by HF/S. When compared with HF/S, HF/6 showed only marginal effects on adipose tissue inflammation. However, inclusion of n-3 PUFA in the diet (HF/3) completely prevented macrophage infiltration induced by high-fat diet and changes in inflammatory gene expression, also tending to reduce JNK phosphorylation (p<0.1) in diabetic mice despite unreduced body weight. Moreover, high-fat diets (HF/S, HF/6) downregulated expression and reduced serum concentrations of adiponectin, but this was not the case with n-3 PUFA.

Conclusions/interpretation: n-3 PUFA prevent adipose tissue inflammation induced by high-fat diet in obese diabetic mice, thereby dissecting obesity from adipose tissue inflammation. These data suggest that beneficial effects of n-3 PUFA on diabetes development could be mediated by their effect on adipose tissue inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / metabolism
  • Adipose Tissue, White / immunology
  • Adipose Tissue, White / metabolism
  • Adipose Tissue, White / pathology*
  • Animals
  • Body Weight / drug effects
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / prevention & control
  • Dietary Fats / administration & dosage
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fluorescent Antibody Technique
  • Gene Expression Profiling / methods
  • Immunoblotting
  • Inflammation / etiology
  • Inflammation / genetics
  • Inflammation / prevention & control*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Obese
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / prevention & control*
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction


  • Adiponectin
  • Dietary Fats
  • Fatty Acids, Omega-3
  • JNK Mitogen-Activated Protein Kinases