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Updated: Aug 7, 2026
An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes
Published on: April 26, 2019
Adipose tissue inflammation induced by high-fat diet in obese diabetic mice is prevented by n-3 polyunsaturated fatty
J Todoric1, M Löffler, J Huber
1Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
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.
