Increased Whole Body -hydroxy--methylbutyrate Production in Chronic Obstructive Pulmonary Disease
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abstract
We have previously observed increased wholebody leucine (LEU) turnover in patients with chronic obstructive pulmonary disease (COPD). hydroxymethylbutyrate (HMB), a product of LEU oxidation, has been shown to accumulate in urine in metabolic diseases such as type 2 diabetes and isovaleric acidemia. In order to examine whether elevated LEU turnover relates to changes in HMB production, we measured fractional synthesis and absolute production rates of HMB in plasma of 12 normal weight COPD patients with moderate to severe airflow obstruction (BMI: 26.95.4 kg/m2, FEV1: 41.714.4%pred.) and 14 healthy, agematched controls (BMI: 27.20.9 kg/m2). Fractional synthesis and absolute production of HMB were assessed by IV administration of a pulse of L[5,5,52H3]leucine followed by GC/MS/MS measurement of plasma concentration and enrichment. Data are summarized by their means SEM and significancetested using Student's ttest for independent samples. Fractional synthesis rate of HMB was similar between groups (CON: 0.09850.012 vs. COPD: 0.1240.019 per hour, P=0.279). Absolute production rates of HMB tended to be greater (P=0.08) for COPD (2.610.50 mol/L/h) than for CON (1.590.25 mol/L/h). In conclusion, the increase in LEU turnover in COPD tends to result in an increase in absolute production of HMB.
