In vivo nitric oxide synthesis, insulin sensitivity, and asymmetric dimethylarginine in obese subjects without and with metabolic syndrome

Abstract

Metabolic syndrome (MetSyn) is associated with impaired endothelial function. Here the association between nitric oxide (NO) production and insulin sensitivity (Si) in obese subjects with and without MetSyn was evaluated. The relationship between NO production and asymmetric dimethylarginine (ADMA) was also explored. Seven healthy normal-weight subjects (male/female [M/F], 3/4; age, 27.4 ± 10.9 years; body mass index [BMI], 21.9 ± 2.2 kg/m2), 7 obese subjects without MetSyn (M/F, 1/6; age, 48.0 ± 8.0 years; BMI, 34.5 ± 2.3 kg/m2), and 7 with MetSyn (M/F, 3/4; age, 48.0 ± 10.7 years; BMI, 33.4 ± 2.9 kg/m2) were recruited. Body composition and cardiometabolic functions (blood pressure, glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein, ADMA) were measured. A frequent sampling intravenous glucose tolerance test was performed to measure Si. A novel stable isotopic method was used to measure in vivo rates of NO production. The NO production was lower in obese subjects with MetSyn compared with normal-weight subjects and obese subjects without MetSyn. Similarly, Si was significantly lower in obesity, both without and with MetSyn, compared with the control group. A significant direct association was found between NO synthesis and Si (ρ = 0.47, P = .03). Circulating levels of ADMA were significantly higher in the obese group with MetSyn. A nonsignificant negative trend between ADMA and NO synthesis was observed. The association between Si and NO production suggests a close mechanistic link between endothelial function and insulin signaling. The results may be highly informative for the development of controlled longitudinal interventions to improve endothelial and metabolic regulation.