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

Abstract

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 effect on the doubly-labelled water (DLW) method for measuring energy expenditure. Synthesis was measured by 2 H incorporation over 14 d in six adult males in approximate energy balance following noradrenaline infusion to maximize mobilization of free fatty acid from adipose tissue. The inter-individual variation in synthesis rates was large and in one subject the proportion 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 subject was five times that of the rest of the group indicating likely violation 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 esterified cholesterol had been synthesized de novo. A high rate of synthesis correlated with a low pre-dose 2 H abundance both within and between lipid classes suggesting that natural 2 H abundance variations in some lipid classes may be used to determine their metabolic origin. Whole-body synthetic rates were 8 g/d for fatty acid and 0⋅3-0⋅5 g/d for cholesterol. These values correspond to very small errors on DLW-derived estimates of CO 2 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 and cholesterol content that the typical Western diet, suggest that the DLW method is unlikely to be affected by fatty acid and cholesterol synthesis in subjects in energy balance consuming a typical Western diet. Deuterium: Doubly-labelled water: Energy expenditure: Lipid synthesisA basic assumption of the doubly-labelled water (DLW) method of measuring energy expenditure is that the H of body water only leaves the body water pool in the form of water (Lifson & McLintock, 1966). If deuterium ( 2 H) was sequestered into products other than water during the course of a DLW study, this would result in an overestimate of water turnover and an underestimate of CO 2 production (Haggarty, 1990) and it is 2 H incorporation into body fat in particular which has the greatest potential to affect the accuracy of the DLW method (Haggarty, 1990). We have previously shown, by direct measurement of 2 H incorporation into body fat, that the process of sequestration can result in an error on the DLW method of −8 % in rapidly growing pigs. This is a significant effect and, if repeated in human subjects, would represent a potentially serious error in the determination of energy requirements and even in relative measurements when comparing DLW-derived estimates of energy expenditure between groups with different intrinsic rates of fat synthesis. Simple estimates of fat deposition cannot be used to estimate sequest...

Effect of photoperiod on body mass, food intake and body composition in the field vole,Microtus agrestis

“…This relative 2 H depletion in lipid has been reported previously (e.g. Haggarty et al, 2000) and is the result of isotope discrimination against heavy hydrogen during reductive biosynthesis of fatty acids (Jungas, 1968).…”

“…of fatty acids and body water in unlabelled animals. The constant 0.53 is the factor accounting for the partial incorporation (18 H) of hydrogen atoms of average fatty acids (34 H) from body water (Jungas, 1968;Guo et al, 2000;Haggarty et al, 2000). Our estimate of de novo lipogenesis includes all fatty acids synthesized from carbohydrates that were accumulated in adipose tissue over 14·days.…”

Mitochondrial Dysfunction and Insulin Resistance: The Contribution of Dioxin-Like Substances

“…This is significant and presents a potentially serious error in the determination of energy requirements, especially in those subjects with different intrinsic rates of fat synthesis. Haggarty et al [17] reported de novo lipogenesis and cholesterol synthesis over the typical duration of a DLW study (2 weeks), as well as the likely effects of sequestration on the performance of the DLW method in adult human subjects.…”

The Endoplasmic Reticulum Coat Protein II Transport Machinery Coordinates Cellular Lipid Secretion and Cholesterol Biosynthesis

“…Indeed, Western-type diets provide ∼400 mg of cholesterol per day, and our bodies synthesize ∼1 g de novo (21, 22). Hence, blood cholesterol levels reflect both dietary and endogenously synthesized cholesterol.…”