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Comparative Study
. 2016 Apr 15;310(8):R744-51.
doi: 10.1152/ajpregu.00473.2015. Epub 2016 Feb 10.

Ablation of eNOS Does Not Promote Adipose Tissue Inflammation

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Free PMC article
Comparative Study

Ablation of eNOS Does Not Promote Adipose Tissue Inflammation

Thomas J Jurrissen et al. Am J Physiol Regul Integr Comp Physiol. .
Free PMC article

Abstract

Adipose tissue (AT) inflammation is a hallmark characteristic of obesity and an important determinant of insulin resistance and cardiovascular disease; therefore, a better understanding of factors regulating AT inflammation is critical. It is well established that reduced vascular endothelial nitric oxide (NO) bioavailability promotes arterial inflammation; however, the role of NO in modulating inflammation in AT remains disputed. In the present study, 10-wk-old C57BL6 wild-type and endothelial nitric oxide synthase (eNOS) knockout male mice were randomized to either a control diet (10% kcal from fat) or a Western diet (44.9% kcal from fat, 17% sucrose, and 1% cholesterol) for 18 wk (n= 7 or 8/group). In wild-type mice, Western diet-induced obesity led to increased visceral white AT expression of inflammatory genes (e.g., MCP1, TNF-α, and CCL5 mRNAs) and markers of macrophage infiltration (e.g., CD68, ITGAM, EMR1, CD11C mRNAs, and Mac-2 protein), as well as reduced markers of mitochondrial content (e.g., OXPHOS complex I and IV protein). Unexpectedly, these effects of Western diet on visceral white AT were not accompanied by decreases in eNOS phosphorylation at Ser-1177 or increases in eNOS phosphorylation at Thr-495. Also counter to expectations, eNOS knockout mice, independent of the diet, were leaner and did not exhibit greater white or brown AT inflammation compared with wild-type mice. Collectively, these findings do not support the hypothesis that reduced NO production from eNOS contributes to obesity-related AT inflammation.

Keywords: Western diet; adipose tissue; endothelial nitric oxide synthase; obesity.

Figures

Fig. 1.
Fig. 1.
Body weight (A), percent body fat (B), epididymal adipose tissue (AT) weight (C), retroperitoneal AT weight (D), interscapular brown AT weight (E), and kilocalories consumed per week (F) in wild-type and eNOS knockout mice fed a control diet vs. Western diet. Values for reported body weight, percent fat, and fat pad weights are from the time of death. Values for kilocalories consumed/week are calculated as an average over the 18-wk feeding period. Data are expressed as means ± SE. D denotes main effect of diet, G denotes main effect of genotype, and D×G denotes diet by genotype interaction. Significant P values (<0.05) are highlighted in bold; n = 7 to 8/group.
Fig. 2.
Fig. 2.
Representative histology images (×10) of visceral white (i.e., epididymal) AT stained for Mac-2 (A), fold differences in Mac-2-positive stained area (B), and average adipocyte size (C) in wild-type and eNOS knockout mice fed a control diet vs. Western diet. Data are expressed as means ± SE. D denotes main effect of diet, G denotes main effect of genotype, D×G denotes diet by genotype interaction. Significant P values (<0.05) are highlighted in bold; n = 5/group.
Fig. 3.
Fig. 3.
Visceral white (i.e., epididymal) (A) and brown (i.e., interscapular) (B) AT gene expression in wild-type and eNOS knockout mice fed a control diet vs. Western diet. Data are expressed as means ± SE. D denotes main effect of diet (P < 0.05). No significant main effects of genotype or interactions were found (all P > 0.05); n = 7 to 8/group.
Fig. 4.
Fig. 4.
Visceral white (i.e., epididymal) AT protein content in wild-type and eNOS knockout mice fed a control diet vs. Western diet. Data are expressed as means ± SE. D denotes main effect of diet, G denotes main effect of genotype, D×G denotes diet by genotype interaction. Significant P values (<0.05) are highlighted in bold; n = 7 to 8/group. For the nitrotyrosine blot, an average of all bands (between 75 kDa and 25 kDa) was calculated.
Fig. 5.
Fig. 5.
Aorta gene expression in wild-type and eNOS knockout mice fed a control diet vs. Western diet. Data are expressed as means ± SE. G denotes main effect of genotype (P < 0.05). No significant main effects of diet or interactions were found (all P > 0.05); n = 4 to 8/group.

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