Free and esterified fatty acid and cholesterol synthesis in adult malesandits effect on the doubly-labelled water method

The purpose of the present study was to estimate whole-body fatty acid and cholesterol synthesis in weight-stable adults and to determine the likely e ffect on the doubly-labelled water (DLW) method for measuring energy expend iture. Synthesis was measured by H-2 incorporation over 14 d in six adult m ales in approximate energy balance following noradrenaline infusion to maxi mize mobilization of free fatty acid from adipose tissue. The inter-individ ual variation in synthesis rates was large and in one subject the proportio n of free fatty acid synthesized was ten times that of the mean of the rest of the group; the fasting concentration of esterified fatty acid in this s ubject was five times that of the rest of the group indicating likely viola tion of the assumptions underlying the calculation of whole-body synthesis. After 14 d of labelling in the other five subjects, 0.9 (sem 0.3) % of the circulating free fatty acid, 9.3 (sem 3.0) % of the esterified fatty acid, 14.6 (sem 2.4) % of the free cholesterol and 28.3 (sem 3.7) % of esterifie d cholesterol had been synthesized de novo. A high rate of synthesis correl ated with a low pre-dose H-2 abundance both within and between lipid classe s suggesting that natural H-2 abundance variations in some lipid classes ma y be used to determine their metabolic origin. Whole-body synthetic rates w ere 8 g/d for fatty acid and 0.3-0.5 g/d for cholesterol. These values corr espond to very small errors on DLW-derived estimates of CO2 production; -2. 5 litres/d for fatty acid and -0.1 to -0.2 litres/d for cholesterol. These results, obtained in subjects typically consuming a diet with a lower fat a nd cholesterol content that the typical Western diet, suggest that the DLW method is unlikely to be affected by fatty acid and cholesterol synthesis i n subjects in energy balance consuming a typical Western diet.