Protein turnover and energy expenditure increase during exogenous nutrient availability in sickle cell disease

Abstract

In the present study, energy expenditure (EE) and rates of whole-body protein, glucose, and lipid metabolism were assessed in 8 African American sickle cell disease (SCD) patients and in 6 healthy African American control subjects during the infusion of amino acids, glucose, and lipid. Wholebody protein, glucose, and lipid kinetics were estimated by using L-[1-13 C]leucine, D-[6,6-2 H 2 ]glucose, and [ 2 H 5 ]glycerol, respectively. After a 2-h tracer equilibration period and a 0.5-h basal period, nutrients were administered intravenously for 3 h with 16% of the energy as protein, 52% as carbohydrate, and 32% as fat. Breath and blood were collected during the last 30 min of nutrient infusion and EE was measured by indirect calorimetry. EE was 14% greater (P ≤ 0.05) in SCD patients [145.0 ± 3.5 kJ · kg fat-free mass (FFM). Whole-body protein breakdown (4.4 ± 0.4 compared with 3.1 ± 0.1 mg · kg FFM Ϫ1 · min Ϫ1 , P ≤ 0.05) and protein synthesis (4.6 ± 0.4 compared with 3.2 ± 0.1 g · kg FFM Ϫ1 · min Ϫ1 , P ≤ 0.05) were 42% and 44% greater, respectively, in the SCD patients than in control subjects, but whole-body amino acid oxidation (0.90 ± 0.05 compared with 1.03 ± 0.09 mg · kg FFM Ϫ1 · min Ϫ1 ) was not significantly different between the 2 groups. Wholebody glucose and lipid kinetics did not differ significantly between the groups. EE increased in SCD patients during exogenous nutrient availability, and the additional energy required for the accelerated rates of whole-body protein breakdown and synthesis made a significant contribution to the increase in EE. These metabolic aberrations may increase the dietary energy and protein requirements of SCD patients.

Erythropoiesis and Myocardial Energy Requirements Contribute to the Hypermetabolism of Childhood Sickle Cell Anemia

“…2F-I), emphasizing that most of the hypermetabolism measured in HbSS may result from compensation for the hemolytic anemia. Our data concur with speculation that erythropoiesis and/or anemia may have specific roles in increasing Q and ultimately, REE (3,6). This observation is consistent with the report from Badaloo et al (30) in which splenectomy normalized both elevated protein turnover and REE in children (HbSS group) with hypersplenism, a condition that further increases the hemolytic rate in children with HbSS.…”

“…Whole-body leucine kinetics were measured by simultaneous administration of [1][2][3][4][5][6][7][8][9][10][11][12][13] (19). Two intravenous catheters were placed in opposite arms, one for infusion of labeled compounds and the other for blood sampling.…”

Energy Expenditure, Inflammation, and Oxidative Stress in Steady-State Adolescents With Sickle Cell Anemia

“…Postulated mechanisms of this increase include elevated cardiac output, necessitated by the low oxygen-carrying capacity of the blood and increased protein turnover in HbSS (20,33). We have estimated that approximately 50% of the increase in REE is due to increased protein synthesis requirements (34). This study shows that REE is correlated with biomarkers of both chronic inflammation (IL-8) and oxidation (F2-IsoPM), and thus these factors may contribute to the increased REE in steady-state adolescents with HbSS.…”

Nutritional status, hospitalization and mortality among patients with sickle cell anemia in Tanzania

“…3 Energy and nutrient supplies are likely to be limited or compromised in SCA by a combination of factors: (i) reduced intake 4 potentially from the anorexic effects of comorbidities; 5 (ii) decreased absorption of nutrients; (iii) increased degradation and losses of nutrients; 6 increased requirements from an elevated basal metabolic rate; 7 and alterations in metabolic pathways. 8,9 Poor growth has been previously documented in SCA. [10][11][12] However, the causes and clinical significance are not well understood.…”