Obesity- and Sex-Related Disturbances in Arginine and Nitric Oxide Kinetics
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AbstractObjectivesArginine (Arg) is considered a conditionally essential amino acid (AA) in the state of inflammation because of its role in nitric oxide (NO) production. NO is emerging as a regulator of energy metabolism and body composition. Although a growing interest exists in supplementation of Arg and citrulline (Cit) because of their potential anti-obesity effects, there is no consensus on the physiological effects of obesity on Arg metabolism and the role of sex.Methods163 subjects were stratified based on their BMI (2030vs<30kg/m2)into normal-to-overweight (n=83, age 49.5 [44.4, 54.5] y, BMI=25.2 [24.36, 25.8] kg/m2) and obese (n=80, age: 54.0 [5.07, 57.3] y, BMI=38.2 [36.9, 39.6] kg/m2) groups. In the overnight fasted state, we collected from each subject arterialized blood for analysis of concentrations of plasma AA, C-reactive protein (CRP as a marker of systemic inflammation), and glucose. We subsequently administered a pulse of AA stable tracers containing Arg, Cit, and ornithine (Orn) and measured their whole-body productions (WBP), calculated their clearance, and the conversions of Arg to Cit (a marker of NO synthesis), Cit to Arg (de novo Arg production), and Arg to Orn (a surrogate of urea production). We measured body composition by DXA. Statistics by ANCOVA adjusted for age, sex, and lean body mass. Data are mean [95% CI]. Significance at P>0.05.ResultsThe obese subjects were characterized by higher CRP (P>0.0001) but comparable fasting glucose levels (P=0.0884) as the normal-to-overweight subjects. We found reduced plasma Cit concentration (P>0.0001) in the obese group and upregulated whole-body clearance of Arg (P=0.0002), Cit (P>0.0001), and Orn (P=0.0002) but no differences in their WBP. We observed elevated production of NO (P>0.0001) in the obese but reduced de novo Arg synthesis (P=0.0007). Females had lower plasma Arg and Orn concentrations, WBP, and clearance of Arg, Cit, and Orn than the males (p>0.05) but comparable Cit concentration and NO production. Obese females had 3.5-fold higher NO production (P=0.0020) than obese males concomitant with a 40% decrease in de novo Arg production (P=0.0059).ConclusionsPlasma Cit is lower in obesity despite enhanced NO production and is related to reduced de novo Arg synthesis. Arg might be considered an essential amino acid in obese women.Funding SourcesNone.
