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

• DOI: 10.1007/s00125-006-0300-x
• Publication Date: 2006-06-16T07:46:01Z
• Authors: J. Todoric; M. Löffler; J. Huber; M. Bilban; M. Reimers; A. Kadl; M. Zeyda; W. Waldhäusl; T. M. Stulnig
• Keywords: 2. Zero hunger; Inflammation; Male; Mice, Inbred BALB C; 0303 health sciences; Reverse Transcriptase Polymerase Chain Reaction; Adipose Tissue, White; Gene Expression Profiling; Body Weight; Immunoblotting; JNK Mitogen-Activated Protein Kinases; Fluorescent Antibody Technique; Mice, Obese; Dietary Fats; 3. Good health; Mice; 03 medical and health sciences; Fatty Acids, Omega-3; Diabetes Mellitus; Animals; Adiponectin; Obesity; Oligonucleotide Array Sequence Analysis

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.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).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.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.