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ORIGINAL RESEARCH COMMUNICATION |
1 From the Department of Food Science and Nutrition, University of Minnesota, St Paul.
2 Supported by a grant from the International Life Sciences Institute–North America and by grant M01-RR00400 from the NCRR/NIH General Clinical Research Center Program.
3 Reprints not available. Address correspondence to EJ Parks, Department of Food Science and Nutrition, University of Minnesota, 1334 Eckles Avenue, St Paul, MN 55108. E-mail: eparks{at}umn.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Objective: The objective was to quantify the diurnal pattern of lipogenesis after 2 consecutive mixed meals were fed to healthy men (n = 8).
Design: A liquid diet was administered after a 12-h fast. During the fasting and postprandial periods, serum insulin, glucose, triacylglycerol, and nonesterified fatty acid concentrations were measured, and rates of DNL were quantified via intravenous infusion of [1-13C] sodium acetate and mass isotopomer distribution analysis.
Results: The temporal pattern of postprandial lipogenesis was similar in all subjects. Lipogenesis rose significantly from 4.7 ± 3.3% at fasting, peaked at 18.2 ± 7.1% after meal 1 (P = 0.003 compared with fasting), rose further to 23.1 ± 8.9% after meal 2 (P = 0.01 for difference between meals), and then decreased toward baseline (P < 0.001). Lipogenesis peaked 4.2 h after the meals; lipoprotein-triacylglycerol concentrations peaked sooner, 2.0 h after the meals (P < 0.02). Maximum postprandial DNL ranged from 10.3% to 37.5%. Peak insulin concentrations after meal 1 correlated with peak DNL (R = 0.838, P = 0.037), although the leanest subjects had some of the highest rates of postprandial DNL.
Conclusion: These data confirm the acute stimulation of DNL after meals in healthy subjects and validate the contribution of this pathway to elevations in triacylglycerol concentration.
Key Words: De novo lipogenesis • hepatic lipogenesis • triacylglycerol
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Previous studies in humans have shown that chronic consumption of diets high in carbohydrate (>50% from mono- and disaccharides) results in a greater amount of newly made fatty acids detected in the blood in fasting persons (12-15). Data are available to document DNL in the fed state; however, the acute effect of food intake immediately after food consumption has not been assessed. Two previous studies measured fed-state lipogenesis after chronic consumption (5–25 d) of high-carbohydrate diets (12, 16). Although average fed-state data were calculated from a selected number of measurements collected on the last day of each study, a pattern of postprandial DNL could not be determined. Another recent study showed higher rates of lipogenesis in obese persons than in lean healthy persons, in both the fasting and fed states, after consumption of a carbohydrate-rich bolus (17). However, fed-state lipogenesis was assessed after only one meal was consumed (80% of energy from carbohydrate) and after only a limited number of postprandial data points were taken, which made it difficult to detect the minute-by-minute pattern of postprandial DNL. Therefore, the immediate effect of eating a mixed meal to stimulate DNL has not been studied. The goals of the present study were two-fold: 1) to document the pattern of postprandial lipogenesis when healthy humans consumed a liquid meal rich in glucose; and 2) to quantify a diurnal pattern of lipogenesis after 2 consecutive meals. Our hypothesis was that lipogenesis would increase acutely after food consumption, but the magnitude of this effect was unknown. To achieve these goals, liquid meals high in monosaccharides were fed.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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48 h. Body composition was determined by dual-energy X-ray absorptiometry (Lunar Corp, Madison, WI). Our original intent was to study both men and women in the immediate postprandial period. By chance, men were the first 3 subjects to be entered into the protocol; in these initial studies, intersubject variability appeared of sufficient magnitude to warrant restriction of subject recruitment to a single sex. To be eligible for the study, subjects had to be aged 20–55 y, be nonsmokers, and have a stable body weight. The subjects maintained consistent exercise and activity patterns for the 3 mo previous to the metabolic study. Subjects were excluded if they had a history of diabetes or any other metabolic disease or if they were taking medication known to affect lipid metabolism.
Study design
Each subject completed a single 24-h inpatient study. For 3 d before this metabolic study, the subject consumed a weight-maintaining diet that provided a constant energy intake based on the Harris-Benedict equation (18) and 3-d food records of usual intake. Because the composition of the diet can significantly affect fatty acid metabolism (19), the goal of the prestudy diet was to provide 55% of total energy from carbohydrate, 30% from fat, and 15% from protein. The actual average profile of the 3-d prestudy diet was as follows: 11840 ± 1590 kJ (51 ± 1% from carbohydrate, 34 ± 0.5% from fat, and 15 ± 1% from protein), 32 ± 9 g fiber, and 7 ± 2 g n–3 fatty acids. Under the direction of a registered dietitian, the diets were prepared by the subjects themselves and consisted of whole foods. On day 1 of the inpatient study, the subject reported to the GCRC between 1630 and 1700. At 1730, 1 intravenous line was placed in the antecubital vein of each arm: one for the administration of stable isotope and the other for blood collection. Between 1800 and 1830, the subject consumed a dinner that met 40% of his total energy needs. The subjects slept overnight at the GCRC and remained in a fasting state until 0700 on day 2, at which time he consumed a liquid meal. A second identical liquid meal was consumed at noon. The liquid formula consumed at breakfast and lunch consisted of an enteral nutritional supplement (Mead Johnson & Company, Evansville, IN), pasteurized egg yolk, heavy whipping cream, and vegetable oil, and was formulated to the same macronutrient composition as the 3-d, prestudy diet. All food components were combined immediately after being heated and were mixed thoroughly for 1 min. To achieve homogeneity, the liquid formula was processed twice via a microfluidizer (model 110Y; Microfluidics Corporation, Newton, MA). The resulting solution was then poured into a covered pitcher and stored at 4 °C. The average total energy provided by the formula was 7900 ± 1449 kJ with a macronutrient profile of 54 ± 1% carbohydrate, 32 ± 1% fat, and 14 ± 0.25% protein. Most of the carbohydrate (99.7%) was glucose, present as maltodextrin in the base formula (Boost; Mead Johnson & Company), and cream provided <0.3% of the carbohydrate as lactose. Of the total percentage of energy coming from carbohydrate, 31% was derived from mono- and disaccharides and 24% was from polysaccharides. The most prominent fatty acids provided by the formula were oleic acid (63%) and linoleic acid (22%); palmitic acid contributed 17% by weight. Each of the 2 meals consumed on day 2 met one-third of the total daily energy requirements of the subjects. The subjects were allowed 60 min to consume each of the 2 liquid meals and, on average, consumed meal 1 in 25 min and meal 2 in 26.5 min. Indirect calorimetry was performed for 30 min from 0630 to 0700 (fasting state) and from 1530 to 1600 (fed state) on day 2 with a Deltatrac II Metabolic Cart (Sensor Medix, Yorba Linda, CA) in the hooded mode. The subjects rested, watched television, or read during the infusion study. Nonenergy-containing, noncaffeinated drinks were available on request.
Metabolic infusion protocol
In all subjects, an intravenous infusion containing sodium [1-13C]acetate (isotopic purity >98%; Cambridge Isotope Laboratories, Andover, MD) was started at 1730 on day 1 and ran until 1800 on day 2. Starting at 0000 and continuing to 1800 on day 2, frequent blood samples were drawn into tubes containing 1 mg EDTA/mL and plasma was separated immediately by centrifugation (3000 rpm, 1500 x g, 10 min, 10 °C). The samples were kept on ice while EDTA, benzamadine, gentamicin sulfate, chloramphenicol, trolox, and phenylmethylsulfonyl fluoride were added as a preservative cocktail (20) and were then portioned for glucose, insulin, and serum triacylglycerol analysis. Plasma samples for nonesterified fatty acid (NEFA) analysis were extracted immediately with a 30:70 heptane:isopropanol mixture containing 10 µL undecanoic acid (11:0) or pentadecanoic acid (15:0) as a fatty acid internal standard (Sigma Chemical Co, St Louis).
Lipoprotein isolation
Lipoprotein isolation and subfractionation of total triacylglycerol-rich lipoproteins (tTRLs), the fraction with a Svedberg flotation unit (Sf) >400 (>400Sf), and the fraction with an Sf of 60–400 (60–400Sf) were performed as described previously (21). Briefly, tTRLs represent all particles with a density <1.0063; the >400Sf fraction contains particles >70 nm in diameter and the 60-400Sf fraction contains particles 40–70 nm in diameter. This method isolates the largest most buoyant particles with a very short half-life and, thus, yields lipogenesis data that reflect the most recently secreted particles by the liver. After separation of the tTRL, >400Sf, and 60–400Sf fractions, fasting and fed apolipoprotein (apo) B-48 and apo B-100 concentrations of each lipoprotein fraction were determined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis to confirm purity of the 60–400Sf fraction (20). Plasma NEFAs and triacylglycerols were separated from the other lipids (phospholipid, cholesterol ester, and free cholesterol) via chromatography and were derivatized to their methyl esters as described previously (21).
Gas chromatography–mass spectrometry and analysis of metabolic variables
The methyl esters of plasma NEFAs and tTRLs (the >400Sf and 60–400Sf fractions) were separated on a Quadrex 007–23 fused silica capillary column, 50 m x 0.25 mm internal diameter x 0.25 µm film thickness (Quadrex Corp, New Haven, CT). Fatty acid composition was measured by flame ionization detection (22). Gas chromatography (GC) was performed on a Hewlett-Packard 5890 instrument (Hewlett-Packard, Norwalk, CT) fitted with a 7683 automatic split injection system and a flame ionization detector. Mass spectrometry (MS) was performed with the use of an HP-1 column (25 m, 250 µm inner diameter x 0.33 µm film thickness) in a Hewlett-Packard 6890 GC (Hewlett-Packard, Eagan, MN) with helium as the carrier gas. Selected ion monitoring was used for ions with mass to charge ratios (m/z) of 270, 271, and 272, which were analyzed with an HP 5973 MS fitted with an ETP electron multiplier (SGE Incorp, Austin, TX). Comparable ion peak areas between an unlabeled standard and biological samples were achieved by either adjusting the volume injected, diluting, or concentrating the sample when needed. Newly made fatty acids from DNL were calculated by mass isotopomer distribution analysis (23). Concentrations of glucose in plasma samples were measured with a Vitros Analyzer 950 (Ortho-Clinical Diagnostics, Rochester, NY) and concentrations of insulin were determined via chemiluminescent immunoassay (Diagnostic Products Corporation, Los Angeles). Serum triacylglycerol and NEFA concentrations were determined via enzymatic assay (Wako Chemicals USA Inc, Richmond, VA) with a microtiter spectrophotometer (model EL 340 Microplate; Bio-Tek Instruments Inc, Winooski, VT).
Calculations and statistical analysis
Individual data from each subject were plotted and evaluated qualitatively, and the general pattern was described. Values for the metabolic variables (eg, triacylglycerol and glucose) attained over the 11-h feeding period were analyzed quantitatively to obtain averages, time to peak height, and rate of increases or decreases (slope), etc. Statistical analyses were performed with the use of STATVIEW for WINDOWS (version 5.0.1; SAS Institute Inc, Berkeley, CA). Differences between the fasting- and fed-state data were analyzed with the use of paired Student's t test. Correlations were analyzed by using simple regression, and the effects of time were analyzed with the use of multiple regression.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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and reflect healthy body weights and normal fasting plasma insulin, glucose, and triacylglycerol concentrations at screening. The changes in insulin, glucose, triacylglycerol, and NEFA concentrations between fasting and feeding are shown in Table 2. As expected, glucose and insulin concentrations averaged over the fasting and the fed states were higher with feeding. Peak concentrations of insulin reached after each meal indicated a significantly greater response after meal 1 (759.3 ± 378.0 pmol/L) than after meal 2 (437.7 ± 182.8 pmol/L; P = 0.006). No significant difference between the 2 meals was found for peak concentrations of glucose. Average concentrations of triacylglycerol in all lipoprotein fractions were higher with feeding (P < 0.03). Peak triacylglycerol concentrations in the tTRL also tended to be higher after meal 2 than after meal 1 (P = 0.066). For the >400Sf fraction, no significant difference between meal peaks was found; the same was true for the 60–400Sf fraction. The concentration of NEFAs tended to drop from the fasting to the fed states, with greater suppression after meal 1 (nadir: 0.14 ± 0.03 mmol/L) than after meal 2 (0.17 ± 0.08 mmol/L). Energy expenditure increased with feeding from 4.60 ± 0.59 kJ · kg–1 · min–1 in the fasting state to 5.23 ± 1.00 kJ · kg–1 · min–1 in the fed state (P = 0.024), as was expected. Fat oxidation was 0.62 ± 0.20 and 0.51 ± 0.39 mg · kg–1 · min–1 (P = 0.340) and glucose oxidation was 0.85 ± 0.51 and 1.16 ± 0.80 mg · kg–1 · min–1 (P = 0.214) in the fasting and fed states, respectively.
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. In the first 2 subjects studied, only tTRLs were isolated. Subject 1 (Figure 1A) had a minimal change in DNL after meal 1, and lipogenesis reached a peak value of only 3.9% 4 h after meal 2. Subject 2 (Figure 1B) had higher DNL throughout the night (note the different scales on the y axis between the subjects) and had higher fed levels of DNL, with fed-state peak values reaching 28.8% 4 h after meal 1 and 29.9% 3 h after meal 2. It was possible that the observed difference in lipogenic rates between these 2 subjects could have been due to a difference in the quantity of remnants present in the tTRL fractions. To remove this potential confounding effect, tTRL particles underwent an additional fractionation step for the remainder of the study, and lipogenesis was measured in the 60–400Sf fraction because this procedure isolates a purer VLDL fraction (which reflects hepatic lipogenic rates). Lipogenesis was also measured in the >400Sf fraction (a combined fraction of chylomicrons and large VLDLs). The lipogenesis data for 60–400Sf fraction only in the remaining 6 subjects are presented individually in Figure 1, C-H, and mean data for all fractions are shown in Figure 2. Although the general pattern of DNL was not different between subjects (Figure 1, C-H), the maximal level of lipogenesis achieved varied between subjects, ranging from 10.3% to 29.8% after meal 1 and from 14.1% to 37.5% after meal 2. Toward the end of the metabolic test, DNL was decreasing in all but one subject (Figure 1E). Surprisingly, the 2 subjects with the lowest percentage body fat had the highest levels of fed-state DNL in the 60–400Sf fraction (Figure 1, B and F). At the time of the study, subject 6 was actively engaged in aerobic activity on a recreational basis 5 times/wk, which put him at the upper end of our study inclusion criteria. This anecdotal information suggests that his high fitness level may have been associated with an increased capacity to make fat. The average values of all subjects showed that newly made triacylglycerol fatty acids in tTRLs and in the 60–400Sf fraction decreased significantly throughout the night (Figure 2; time effect: P < 0.0001). However, after consumption of meal 1, the rate of appearance of newly made fatty acids in the tTRL and the 60–400Sf fraction increased significantly from 1.5 to 4 h (P < 0.0001) and then began to decrease at 4.5 h. The pattern appeared similar but had a shorter initial lag period after meal 2, for which the rate of increase in tTRL and in the 60–400Sf fraction significantly increased from 1.5 to 3 h postmeal (P < 0.0001). During the last 3 h of the metabolic study, DNL decreased significantly in all fractions (P < 0.0001). As shown in Figure 2, the postprandial <60–400Sf fraction contained a larger percentage of newly made fatty acids than did the other 2 fractions. DNL in tTRLs averaged 
75% of the DNL in the 60–400Sf fraction. The fed-state percentage of DNL in the 60–400Sf fraction correlated significantly with DNL in tTRLs (R = 0.949, P = 0.004; data not shown). At its highest peak, DNL in the >400Sf fraction reached a value of only 7.2 ± 3.7%, whereas DNL in the 60–400Sf fraction peaked at 18.2 ± 7.2% after meal 1 and 23.1 ± 8.9% after meal 2. The temporal pattern of concentrations in the 60–400Sf triacylglycerols is shown in Figure 2. Newly made fatty acids were rising gradually as triacylglycerol concentrations fell.
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; P = 0.125). Peak DNL values achieved after meal 2 in all triacylglycerol fractions were significantly higher than those after meal 1 (Table 2 and Figure 2). For the 60–400Sf fraction specifically, DNL was 27% higher after meal 2. The times to peak DNL in tTRLs, in the >400Sf fraction, and in the 60–400Sf fraction were 4.4, 3.3, and 4.3 h, respectively, after meal 1 and 4.0, 3.6, and 4.2 h after meal 2. For the 60–400sf, the time to peak DNL between the 2 meals was not significantly different (P = 0.664), whereas the time to peak triacylglycerol concentration in this fraction was significantly shorter after meal 2 than after meal 1 (1.3 compared with 2.7 h, respectively; P = 0.016; Figure 2).
Correlations
In the present study, the magnitude of the peak insulin concentration after meal 1 correlated with peak DNL in the 60–400Sf fraction (R = 0.838, P = 0.037). After meal 2, peak insulin concentrations positively correlated with peak triacylglycerol concentration in tTRLs (R = 0.753) and in the >400Sf fraction (R = 0.915, P < 0.03 for both); insulin failed to correlate with lipogenesis in any fraction after meal 2. Data from previous studies showed a positive correlation between an increase in fasting DNL in VLDLs associated with chronic consumption of high-carbohydrate diets and changes in fasting triacylglycerol concentrations (14, 15). Specifically, Schwarz et al (15) found that the increase in the fasting percentage of DNL correlated with the percentage increase in fasting triacylglycerol concentrations associated with 5 d of a high-carbohydrate diet (R = 0.932, P < 0.05). In the present study, a positive relation was also found between fasting DNL in the 60–400Sf fraction and the acute increase in triacylglycerol after meal 1 (R = 0.860, P < 0.03). These observations relate to the level of lipogenesis in the fasting state in these subjects and to changes in triacylglycerol concentration after the liquid meal. However, if lipogenesis contributes directly to increases in triacylglycerol concentrations postprandially, the acute change in DNL after a meal should correlate with the change in triacylglycerol concentration after that meal. Surprisingly, when this relation was tested in the present study, a negative correlation was found (R = –0.888, P = 0.018) (Figure 3).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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First, DNL rose significantly after meal 1 and further increased after meal 2; the second peak was 27% greater than the first peak. These observations more completely define the effect of meals originally suggested by the diurnal pattern of Hudgins et al (14), who found progressively higher daylong rates of lipogenesis based on data obtained intermittently over a 24-h period. Our data also expand on the data of Hellerstein et al (24), who fed healthy subjects either hourly boluses of liquid formula or a solid breakfast meal, and on the data of Marques-Lopes et al (17), who similarly showed minor increases in DNL after a carbohydrate-rich meal bolus. During feeding, lipogenesis rose from 1% (fasting) to 5% (fed) in lean persons in both studies and from 3% to 9% in the obese subjects studied by Marques-Lopes. Both studies fed more carbohydrate (159-245 g) than that fed in the present study (125 g/bolus); however, we observed much higher rates of lipogenesis (23%). One likely reason for this discrepancy is because the acetate infusion in the present study began 14 h before the fed-state measurements were made, whereas these other studies infused acetate for 7–9 h before the first measurement. The present data support the concept that a longer duration of labeling is necessary to equilibrate newly made fatty acid pools in the liver (12). Another factor that contributed to the higher peak values observed in the present study was the method of lipid fractionation that we used (21). Without this procedure, most of the particles in the tTRL fraction would be VLDL remnants and intermediate-density lipoproteins, whose turnover is 6–8 h (25).
Second, as shown here, measurement of the temporal pattern showed that the largest absolute contribution of newly made fatty acids to VLDL-triacylglycerol occurred toward the end of the metabolic test (11 h), at which time triacylglycerol concentrations were decreasing faster than was lipogenesis (Figure 2). After both meals, postprandial triacylglycerol concentration peaked roughly between 2 and 3 h postmeal, a consistent finding in the literature (1, 5, 26-28), whereas peak DNL occurred slightly >4 h postmeal. This delayed pattern of DNL after meal 1 was consistent with the time delay for sensitization of the liver to up-regulate fatty acid synthase enzyme as a result of an early elevation in insulin concentration. In the present study, the change in insulin concentration postprandially correlated positively with the change in hepatic lipogenesis after meal 1. Furthermore, we found a negative correlation between the percentage increase in DNL and the absolute increase in triacylglycerol concentration (Figure 3). Thus, larger increases in postprandial triacylglycerol were associated with smaller increases in the percentage of newly made fatty acids in VLDL-triacylglycerol early in the postprandial period. Meal 2 resulted in much lower insulin peaks, as has been observed previously (29). Despite the lower insulin response after meal 2, the percentage of newly made fatty acids was 27% higher after meal 2. Interestingly, the significant association between insulin and DNL was lost after meal 2, as was the negative correlation between the change in triacylglycerol concentration and the change in DNL. This could have resulted from the presence of remnants, because observations from independent studies are beginning to support the concept that consumption of carbohydrate is associated with an accumulation of remnants in the plasma (21, 30). Because remnants contain substantial amounts of triacylglycerol but few, if any, newly made fatty acids (tTRL and > 400Sf; Figure 2), they would dilute the apparent percentage of DNL in hepatically derived particles. Lastly, although the general pattern of lipogenesis among the subjects was strikingly similar, close inspection of the curves raises critical questions as to the metabolic basis for the differences between subjects.
Factors that can contribute to the variability in lipogenesis between subjects could include differences in the rate of digestion, the time taken to consume the liquid formula, other sources of fatty acids that can contribute to VLDL-triacylglycerol, and the relative caloric balance of the subjects before the metabolic test. Given that the meals were liquid formula, it is likely that the rate of digestion was faster than that with solid food. A fast rate of absorption would tend to increase the observed lipogenic rates and whether individual differences significantly impacted lipogenesis in the present study is unknown. Because the duration of meal consumption was small (25 min) relative to that in the 11-h study, it is unlikely that meal-duration differences between subjects contributed to the variability observed in lipogenesis (Figure 1). DNL is just one of many sources of fatty acids that could contribute to VLDL-triacylglycerol secreted by the liver postprandially. These fatty acid sources (eg, NEFAs, dietary lipid, and splanchnic pools) must all be regulated, and their fluxes may be variably affected by insulin in different subjects. If hepatic or splanchnic triacylglycerol stores were used for VLDL synthesis, it would result in an observed lower level of newly made fatty acids secreted in VLDL. The intrahepatic lipogenic rate may still be up-regulated, but the rate of DNL fatty acids in the blood would appear lower if newly made fatty acids first joined a hepatic triacylglycerol pool that turned over slowly. A final critical factor that can affect a person's lipogenic response to feeding is energy balance—a caloric deficit suppresses DNL, whereas overfeeding increases it (16). To control for this effect, the food intake of subjects was prescribed for the 3 d before the test to maintain energy balance. Furthermore, the amount of energy consumed in the liquid formula during the metabolic test was based on the subject's energy need. Notably, the variability in the present study echoes that observed over a 24-h period by Hudgins et al (14) and remains an important topic for future research.
Although we cannot entirely explain the variability in postprandial DNL observed in our subjects, the results from the present study add substantial knowledge to the area of postprandial lipogenesis. The postprandial design of the study itself is relevant because most of the hours in the day are typically spent in the fed state. As cited above, one limitation of the present study design was the use of liquid meals rather than whole foods (7). However, the use of formula in the present study did provide a model for the stimulation of DNL when energy is provided in liquid form. Second, the frequency of meals in the present study may or may not be relevant when considering individual food intake patterns. The current results cannot discern between the effect on lipogenesis of bolus feeding (ie, 3 meals/d) compared with that of more frequent episodes of eating throughout the day, during which time insulin concentrations remain elevated over a longer duration.
In summary, the present work documents changes in rates of DNL postprandially in healthy men. The stimulation of lipogenesis after meals provided a significant source of fatty acids contributing to blood triacylglycerol, which averaged 23% VLDL-triacylglycerol fatty acids. Given the atherogenicity of the postprandial state, the contribution of DNL to this process requires further study. Identifying the individual factors that alter lipogenesis will be key to understanding how fatty acid synthesis fits into the syndrome of insulin resistance. The importance of DNL in elevating postprandial lipemia will best be delineated when it is quantitated along with the other sources of triacylglycerol in the blood after a meal (eg, NEFAs and dietary fatty acids). This will be the focus of future investigation.
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ACKNOWLEDGMENTS |
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EJP originally designed the study, provided data interpretation, and assisted with the writing of the manuscript. MTT coordinated the clinical research, data collection, technical and statistical analyses, and writing of the manuscript. The authors had no conflicts of interest.
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