Ablation of eNOS does not promote adipose tissue inflammation

Am J Physiol Regul Integr Comp Physiol. 2016 Apr 15;310(8):R744-51. doi: 10.1152/ajpregu.00473.2015. Epub 2016 Feb 10.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue, Brown / enzymology
  • Adiposity
  • Animals
  • Diet, High-Fat
  • Disease Models, Animal
  • Genetic Predisposition to Disease
  • Inflammation Mediators / metabolism
  • Insulin Resistance
  • Intra-Abdominal Fat / enzymology*
  • Macrophages / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondrial Proteins / metabolism
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type III / deficiency*
  • Nitric Oxide Synthase Type III / genetics
  • Obesity / enzymology*
  • Obesity / genetics
  • Obesity / physiopathology
  • Panniculitis / enzymology*
  • Panniculitis / genetics
  • Panniculitis / physiopathology
  • Phenotype
  • Phosphorylation
  • Serine
  • Signal Transduction
  • Threonine


  • Inflammation Mediators
  • Mitochondrial Proteins
  • Threonine
  • Nitric Oxide
  • Serine
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse