eNOS phosphorylation on serine 1176 affects insulin sensitivity and adiposity

► eNOS phosphorylation influences blood pressure, vascular reactivity, and NO bioavailability. ► The phosphomimetic eNOS mutation improves insulin sensitivity and protects against weight gain. ► The unphosphorylatable mutation results in insulin resistance, hypertension, and obesity. ► eNOS phosphorylation at S1176 is a novel target for obesity and insulin resistance.