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


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
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.
Todoric
J
J
Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Löffler
M
M
Huber
J
J
Bilban
M
M
Reimers
M
M
Kadl
A
A
Zeyda
M
M
Waldhäusl
W
W
Stulnig
T M
TM
D052242:Adiponectin / Q000378:metabolism; D052436:Adipose Tissue, White / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003920:Diabetes Mellitus / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D004041:Dietary Fats / Q000008:administration & dosage; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling / Q000379:methods; D015151:Immunoblotting; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008820:Mice, Obese; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D052242:Adiponectin; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D048031:JNK Mitogen-Activated Protein Kinases