ENOS phosphorylation on serine 1176 affects insulin sensitivity and adiposity

Satoshi Kashiwagi, Dmitriy N. Atochin, Qian Li, Michael Schleicher, Terrence Pong, William C. Sessa, Paul L. Huang

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Phosphorylation of endothelial nitric oxide synthase (eNOS) is an important regulator of its enzymatic activity. We generated knockin mice expressing phosphomimetic (SD) and unphosphorylatable (SA) eNOS mutations at S1176 to study the role of eNOS phosphorylation. The single amino acid SA mutation is associated with hypertension and decreased vascular reactivity, while the SD mutation results in increased basal and stimulated endothelial NO production. In addition to these vascular effects, modulation of the S1176 phosphorylation site resulted in unanticipated effects on metabolism. The eNOS SA mutation results in insulin resistance, hyperinsulinemia, adiposity, and increased weight gain on high fat. In contrast, the eNOS SD mutation is associated with decreased insulin levels and resistance to high fat-induced weight gain. These results demonstrate the importance of eNOS in regulation of insulin sensitivity, energy metabolism, and bodyweight regulation, and suggest eNOS phosphorylation as a novel target for the treatment of obesity and insulin resistance.

Original languageEnglish
Pages (from-to)284-290
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 8 Feb 2013
Externally publishedYes


  • Diabetes
  • Endothelium
  • Insulin resistance
  • Metabolism
  • Nitric oxide
  • Obesity

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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