Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity

Abstract

This study determined whether reductions in postprandial plasma nonesterified fatty acid (FFA) flux would lead to reductions in plasma acylcarnitine (AC) concentrations. Plasma AC was measured by liquid chromatography with tandem mass spectrometry in the fasting state and over 6 hours after a high-fat (50% energy) meal was fed to 16 overweight and obese subjects with a wide range of insulin sensitivities. Body composition was measured by dual-energy x-ray absorptiometry; insulin sensitivity by insulin-modified, frequently sampled intravenous glucose tolerance test; substrate oxidation by indirect calorimetry; blood metabolite and hormone concentrations biochemically; and fatty acid flux by using stable isotope tracers. Lean body mass and fasting fat oxidation correlated positively (r > 0.522, P < .05), whereas glucose oxidation correlated negatively (r < -0.551, P < .04), with fasting AC. Postprandially, plasma glucose, insulin, and triglyceride concentrations increased; and FFA concentrations decreased significantly. The responses of plasma AC species depended on chain length and saturation, with C14:0, C16:0, and C18:0 remaining unchanged, and unsaturated species (eg, C14:1, C14:2) falling significantly (21%-46%, P < .03). Postmeal nadir AC concentrations were positively associated with lean body mass, postprandial fatty acid flux, and FFA concentrations (r > 0.515, P < .05). By contrast, nadir AC correlated negatively with insulin sensitivity and spillover of meal-derived fatty acids (r < -0.528, P < .04). Conditions that impact fatty acid flux contribute to the control of postprandial plasma AC concentrations. These data underscore the need for a better understanding of postprandial fatty acid oxidation and dietary fat delivery in the setting of adipose insulin resistance to determine how postprandial lipemia contributes to chronic disease risk.

Conflict of interest statement

Disclosure Statement: No conflicts of interest exist for any of the four authors.

Copyright © 2012 Elsevier Inc. All rights reserved.

Figures

Figure 1. Study Timeline

During the 7-days prior to the study, the subject consumed a standardized diet. The X on the figure denotes the timing of blood draws and RQ denotes the timing of indirect calorimetry.

Figure 2. Concentrations of metabolites and insulin, substrate oxidation, energy expenditure and RaFFA (µmol/kg/min) in the fasted and fed states

N=16, data are mean ± SEM. Subjects had remained fasted from the time of consumption of the previous evening meal at 1800 on day 1. Samples were collected from −6h (0600 h) and the noon meal is denoted by the arrow at time 0. For fig. 2C and 2D, fasted values represent data from −4h and fed data from +2.5h. Fasting and fed RaFFA (fig. 2F, units in µmol total fatty acids /kg total body weight /min) were determined using Steele's equation (see methods). For fig. 2G, presented on the left is a graph of the relationship between fasting C14:2 and the fasting RaFFA (taken at −2h). The table on the right presents the other fasting AC data that also correlated with fasting RaFFA. The symbol * indicates P ≤ 0.05.

Figure 3. Correlations between selected variables and fasting acylcarnitine species

Fig. 3A, depicts the lack of association between variables relevant to carbohydrate metabolism (fasting glucose, HOMA-IR, fasting insulin, SI transformed as the natural logarithm, and HbA1c) and C2. For fig. 3B–3D, presented on the left is a representative graph of the relationship between independent variables (lean body mass, fat oxidation, and glucose oxidation) and AC species. The table on the right presents the other AC data that also correlated with each independent variable of interest.

Figure 4. Fasting and post-meal nadir concentrations of plasma acylcarnitine species

Values are mean ± SEM. Fasting data (open bars), fed nadir concentration (solid bars). * P < 0.05, †P < 0.09.

Figure 5. Correlations between selected variables and post-meal nadir acylcarnitine species

The left side of each figure has a representative graph of the relationship between independent variables (LnSI, nadir RaFFA, nadir FFA concentration, or maximum spillover measured) and nadir AC. The table at the right presents other AC species that also correlated with the variable of interest.