Todoric J, Löffler M, Huber J, Bilban M, Reimers M, Kadl A, Zeyda M, Waldhäusl W, Stulnig T M
Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
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.
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.
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.
目的/假设:白色脂肪组织中的炎症改变似乎是肥胖并发症(包括糖尿病)的基础。多不饱和脂肪酸(PUFA),尤其是n-3系列的多不饱和脂肪酸,可调节免疫反应,并可能改善胰岛素敏感性。在本研究中,我们调查了PUFA如何影响肥胖糖尿病动物的白色脂肪组织炎症和基因表达。
我们用低脂标准饮食(LF)或富含以下成分的高脂饮食对db/db小鼠以及瘦的非糖尿病小鼠(db/+)进行处理:(1)饱和/单不饱和脂肪酸(HF/S)、(2)n-6多不饱和脂肪酸(HF/6)和(3)包含纯化海洋n-3多不饱和脂肪酸的后者(HF/3)。
与LF相比,HF/S喂养的db/db小鼠中许多参与炎症改变的基因上调,同时c-Jun氨基末端激酶(JNK)磷酸化。同时,HF/S显著增强了巨噬细胞对脂肪组织的浸润。与HF/S相比,HF/6对脂肪组织炎症仅产生轻微影响。然而,饮食中添加n-3多不饱和脂肪酸(HF/3)完全阻止了高脂饮食诱导的巨噬细胞浸润和炎症基因表达的变化,尽管体重未减轻,但也倾向于降低糖尿病小鼠的JNK磷酸化(p<0.1)。此外,高脂饮食(HF/S、HF/6)下调了脂联素的表达并降低了血清浓度,但n-3多不饱和脂肪酸并非如此。
结论/解读:n-3多不饱和脂肪酸可预防肥胖糖尿病小鼠中由高脂饮食诱导的脂肪组织炎症,从而将肥胖与脂肪组织炎症区分开来。这些数据表明,n-3多不饱和脂肪酸对糖尿病发展的有益作用可能是通过其对脂肪组织炎症的影响来介导的。