Corticosteroids increase glutamine utilization in human splanchnic bed.

Glutamine is the most abundant amino acid in the body and is extensively taken up in gut and liver in healthy humans. To determine whether glucocorticosteroids alter splanchnic glutamine metabolism, the effect of prednisone was assessed in healthy volunteers using isotope tracer methods. Two groups of healthy adults received 5-h intravenous infusions of l-[1-(14)C]leucine and l-[(2)H(5)]glutamine, along with q. 20 min oral sips of tracer doses of l-[1-(13)C]glutamine in the fasting state, either 1) at baseline (control group; n = 6) or 2) after a 6-day course of 0.8 mg.kg(-1).day(-1) prednisone (prednisone group; n = 8). Leucine and glutamine appearance rates (Ra) were determined from plasma [1-(14)C]ketoisocaproate and [(2)H(5)]glutamine, respectively, and leucine and glutamine oxidation from breath (14)CO(2) and (13)CO(2), respectively. Splanchnic glutamine extraction was estimated by the fraction of orally administered [(13)C]glutamine that failed to appear into systemic blood. Prednisone treatment 1) did not affect leucine Ra or leucine oxidation; 2) increased plasma glutamine Ra, mostly owing to enhanced glutamine de novo synthesis (medians +/- interquartiles, 412 +/- 61 vs. 280 +/- 190 mumol.kg(-1).h(-1), P = 0.003); and 3) increased the fraction of orally administered glutamine undergoing extraction in the splanchnic territory (means +/- SE 64 +/- 6 vs. 42 +/- 12%, P < 0.05), without any change in the fraction of glutamine oxidized (means +/- SE, 75 +/- 4 vs. 77 +/- 4%, not significant). We conclude that high-dose glucocorticosteroids increase in splanchnic bed the glutamine requirements. The role of such changes in patients receiving chronic corticoid treatment for inflammatory diseases or suffering from severe illness remains to be determined.

Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation.

CONTEXT: Retinol binding protein (RBP4), secreted primarily from the liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity, its relationship with subclinical inflammation, and its response to lifestyle changes are not elucidated. OBJECTIVE: The objective of the study was to determine in children: 1) the status of RBP4 levels in lean vs. obese; 2) the relationship between RBP4 levels and subclinical inflammation; and 3) the effect of lifestyle-only intervention on RBP4 levels. DESIGN, SETTING, AND PATIENTS: Lean and obese children (n = 21) matched for age (>14 yr to < 18 yr) and maturity stage (Tanner IV) were studied at baseline and with lifestyle intervention in obese subjects only (n = 15). INTERVENTION: Patients received 3 months of randomized and controlled physical activity-based lifestyle intervention. MAIN OUTCOME MEASURE: RBP4 levels in children before and after intervention and the relationship between RBP4 and subclinical inflammation were measured. RESULTS: Higher RBP4 levels were found in the obese group vs. lean group (P = 0.005). RBP4 correlated with not only indices of obesity and insulin resistance but also inflammatory factors (r = 0.63 and 0.64 for C-reactive protein and IL-6, respectively, P < 0.01). Intervention reduced RBP4 levels by approximately 30% (P = 0.001), and RBP4 reduction was correlated with the magnitude of decrease in inflammatory factors (P = 0.01). CONCLUSION: Alterations in serum RBP4 occur at an early age in the clinical course of obesity and appear to correlate with subclinical inflammation. Lifestyle intervention almost entirely reversed the raised RBP4 levels in obese children. Future studies should determine whether elevation of RBP4 is a direct trigger for the insulin resistance and subclinical inflammation implicated in the premature development of cardiovascular disease and diabetes.