title: Ablation of eNOS does not promote adipose tissue inflammation.
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.
authors: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri;
authors: Thomas J
authors: TJ
authors: Jurrissen
authors: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; Research Service-Harry S. Truman Memorial Veterans Affairs Medical Center, Columbia, Missouri;
authors: Ryan D
authors: RD
authors: Sheldon
authors: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri;
authors: Michelle L
authors: ML
authors: Gastecki
authors: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri;
authors: Makenzie L
authors: ML
authors: Woodford
authors: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri;
authors: Terese M
authors: TM
authors: Zidon
authors: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; Research Service-Harry S. Truman Memorial Veterans Affairs Medical Center, Columbia, Missouri; Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri;
authors: R Scott
authors: RS
authors: Rector
authors: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri;
authors: Victoria J
authors: http://orcid.org/0000-0001-7563-0806
authors: VJ
authors: Vieira-Potter
authors: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri; and Child Health, University of Missouri, Columbia, Missouri padillaja@missouri.edu.
authors: Jaume
authors: J
authors: Padilla
mesh_terms: D002001:Adipose Tissue, Brown / Q000201:enzymology; D050154:Adiposity; D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000201:enzymology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency* / Q000235:genetics; D009765:Obesity / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D015434:Panniculitis / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D010766:Phosphorylation; D012694:Serine; D015398:Signal Transduction; D013912:Threonine
chemical_list: D018836:Inflammation Mediators; D024101:Mitochondrial Proteins; D013912:Threonine; D009569:Nitric Oxide; D012694:Serine; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: Western diet; adipose tissue; endothelial nitric oxide synthase; obesity