Inclusion of n-3 polyunsaturated fatty acids into high-fat diets prevents adipose tissue inflammation in obese diabetic mice

Objectives: Inflammatory changes in white adipose tissue of obese individuals appear to be causally linked to development of insulin resistance and type 2 diabetes mellitus. Based on beneficial effects of n-3 polyunsaturated fatty acids (PUFA) on inflammatory responses and diabetes development, we investigated possible effects of n-3 PUFA on white adipose tissue inflammation in obese diabetic mice.

Methods: Obese diabetic (db/db) as well as lean non-diabetic mice (db/+) were treated with either low-fat standard diet (LF) or high-fat diets enriched in saturated and monounsaturated fatty acids (HF/S), n-6 PUFA (HF/6) and the latter including 30% of fatty acids as n-3 PUFA (HF/3) for 6 weeks. Gene expression was evaluated from db/db and LF db/+ animals by oligonucleotide microarrays and by quantitative RT-PCR.

Results: We found increased expression of a large number of inflammatory genes in db/db animals treated with HF/S or HF/6 compared to those on LF, including CCL2 (MCP-1 gene), CD68, Itagm (complement receptor 3α gene). N-3 PUFA prevented HF-induced changes in inflammatory gene expression. HF strongly promoted macrophage infiltration in adipose tissue in db/db mice as assessed by immunofluorescence analyses on macrophage markers F4/80 and MAC-2 but not in presence of n-3 PUFA (HF/3). Moreover, HF/S resulted in a two-fold activation of the c-jun NH₂-terminal kinase (JNK) activation that was almost completely prevented by HF/3 in db/db mice.

Conclusion: Protective effects of n-3 PUFAs on diabetes development could at least in part be due to their potent anti-inflammatory effect on obesity-associated adipose tissue inflammation.

This work was supported by CeMM – Center of Molecular Medicine, a basic research institute within the companies of the Austrian Academy of Sciences (to T.M.S. and W.W.) and the Joseph Skoda Award of the Austrian Association for Internal Medicine (to T.M.S.).