Subjects and methods

Subjects

A total of 40 women, aged from 30 to 40 y were divided into four groups of 10 according to their BMI(normal: BMI<25, preobese: 25<BMI<30, obese: 30<BMI<40, morbid obese: BMI>40 kg/m²). Exclusion criteria were apparent or reported diseases, amenorrhea, pregnancy or breast-feeding, alcohol abuse, use of antihyperlipemia or antiobesity medications, as well as dietary regimen for weight loss for the last 6 months. All participants were sedentary, were not smokers and none had arterial hypertension.

The design and objective of the study were explained to each participant before the study, and an informed written consent was obtained from each of the individuals. The Scientific and Ethics Committee of the Medical School Heart Institute Hospital of São Paulo University (USP) approved the study.

Emulsion preparation

The emulsion was prepared as previously described,²² with addition to the lipid mixtures of [1-¹⁴C] cholesteryl-oleate (specific activity 2.07 Gbq/mmol) and [9,10-³H] glycerol-trioleate (specific activity 518 GBq/mmol), supplied by Amersham International (UK). The emulsion was purified by two-step ultra centrifugation, as described previously,²³ sterilized by passage through a 0.2 m filter and evaluated for sterility and pyrogenicity prior to injection into the patients.

Kinetics of the emulsion

Determination of chylomicron-like emulsion plasma kinetics was performed in four women groups. The fraction of the emulsion preparation that was injected into each subject contained approximately 3.0 mg total lipid mass in 500 l volume. [¹⁴C] and [³H] radioactivity of the labeled lipids were 74 kBq (2 Ci) and 148 kBq (4.0 Ci), respectively. The emulsion was injected intravenously in a bolus, after 12 h fasting. Blood samples were collected from another peripheral vein at pre-established intervals during 45 min. Blood was centrifuged and the radioactivity contained in 1.0 ml of plasma was measured by 'Liquid Scintillation Counting' (Packard 1.660 TR, Meridien, CT, USA). The safety of the radioactive dose injected into the subjects was warranted according to radioprotection regulations²⁴ as described elsewhere.¹⁷

Compartmental analysis

Emulsion removal from the plasma was evaluated by compartmental analysis according to a modification of the model proposed by Redgrave et al.²⁵ Briefly, four compartments were employed to estimate the kinetic parameters for both ¹⁴C-Cholesteryl-oleate (CO) and ³H-Triolein (TO) tracers. Plasma hydrolysis and removal of native chylomicrons, as well as chylomicron-like emulsions, displayed a rapid initial decay followed by a slow removal phase.^{9, 17, 26} The k_x,y constants represent the transfer or fractional catabolic rates (FCR) from compartment _x to compartment _y. Compartments 1–4 and 5–8 represent the kinetics of cholesterol and triglycerides metabolism, respectively. The rapid and slow decay phases evaluated by the CO and TO tracers are represented, respectively, by k_1,3 and k_2,3 and by k_5,7 and k_6,7. The model also takes into account the recirculation of the radioactive tracers in plasma on the form of newly synthesized VLDL (expressed by k_3,4 and k_7,8 for the ¹⁴C and ³H, respectively). The lipolysis index, which estimates the percentage of TO removed by lipoprotein lipase action, was calculated from the differences between the areas under the curve (AUC) for the removal of CO and TO. All calculations were performed using a computer software.²⁷ Details of the compartmental analysis calculations were published previously.²⁸

Biochemical analysis

Serum triglycerides, total, LDL and HDL cholesterol, apolipoprotein A1 (apo A1) and apoliprotein B (apo B) and glucose were determined from blood samples taken after 12 h fasting using an automatic instrument (Cobas Mira Plus—Roche). Total cholesterol and triglycerides were determined with the aid of enzymatic test kits (CHO-PAD, Boehringer and Abbott, respectively). HDL cholesterol was determined by the same method, after precipitation of LDL and VLDL with MgCl₂, phosphotungstic acid and LDL cholesterol were calculated using the Friedewald equation.²⁹ An oral glucose tolerance test was performed over 2 h after the ingestion of a 75 g glucose load.

Statistical analysis

All recorded variables were tabulated as meanss.d. or s.e.m. The differences in the obtained data were evaluated by one-way ANOVA. When the ANOVA showed significant differences, median values were compared by Kruskal–Wallis nonparametric test. The level of significance was set at P<0.05 for all comparisons. The Pearson product–moment correlation coefficients were used to quantify associations among variables.

Results

Plasma, lipids, apolipoproteins and glucose

Table 1 shows the physical characteristics and the plasma lipid and apoliprotein profile of the four women groups. Total cholesterol values were not different among the groups. HDL cholesterol, however, was progressively lower from normal weight to preobese, obese and morbid obese groups (P<0.05). ApoA1 was lower in morbid obese and preobese compared to the normal weight group. In the obese, this trend did not attain statistical significance. Apolipoprotein B values were greater than the normal weight group in the preobese and morbid obese groups, but not in the obese group. Fasting triglycerides were greater in the obese and morbid obese. All the women groups had fasting glucose plasma concentrations within the normal range. The oral glucose test was performed in the groups of the obese and morbid obese women, but not in the normal weight and preobese groups. The 2 h post 75 g glucose load glycemia was 4.81.04 mmol/l in the obese and 4.321.01 mmol/l in the morbid obese group. No subjects of the obese group and only one of the morbid obese group had 2 h glycemia above the 7.0 mmol/l cutoff level for glucose intolerance.³⁰

Table 1 - Individual physical characteristics, plasma lipid and apolipoprotein profiles (means.d.) in women groups according to BMI.

Full table

Emulsion plasma kinetics

Figure 1 shows the plasma decay curves of the emulsion radioactive lipids obtained from the four study groups. It is apparent that the triolein decay curves of the four groups was not different, but the curves of the cholesteryl oleate were progressively slower in the preobese, obese and morbid obese groups, taking the normal weight curve as reference.

Figure 1.

Removal from the plasma of the emulsion (a) [³H] glycerol trioleate (NS by ANOVA) and (b) [¹⁴C] Cholesteryl-oleate (P<0.003 by ANOVA) in women groups according to BMI.

Full figure and legend (41K)

Table 2 shows the plasma kinetic data calculated from the decay curves. There was no difference among the study groups with regard to the FCR-TO. However, the FCR-CO was smaller in the obese and morbid obese groups compared to the normal weight groups, while preobese values were not different.

Table 2 - Plasma kinetic parameters of the emulsion (means.e.m.) in women groups according to BMI.

Full table

Figure 2 and Table 3 show that the FCR-CO negatively correlates with the BMI of the subjects (r=-0.388; P=0.01). Figure 2 also shows that the FCR-TO of the emulsion did not correlate with BMI, but, nonetheless, there is a positive correlation between the lipolysis index and BMI.

Figure 2.

Correlation between BMI and (a) FCR-TO, (b) FCR-CO and (c) lipolysis.

Full figure and legend (36K)

Table 3 - Correlation between plasma kinetic parameters, BMI and plasma lipid in women (n=40).

Full table

There was also a positive correlation between the FCR-CO with HDL cholesterol (r=0.345; P=0.03), and negative with fast triglycerides (r=-0.428; P=0.005). Correlations between glycemia or plasma tryglyceride and waist circumference with the kinetics of the emulsion-labeled lipids were not found.

Classical correlations of blood lipids and BMI were confirmed in this study, such as the positive correlations of the BMI with fast triglycerides (r=0.496; P=0.001), the negative correlation of the BMI with HDL cholesterol (r=0.683; P=0.0001) and positive correlation of waist circumference with fast triglycerides (r=0.518; P=0.001). Plasma glucose values did not correlate with BMI and waist circumference.

The difference in FCR-CO was largely due to the k_1–3 constant. According to the compartmental model used to analyze data, the k_1–3 constant is related with the first exponential of the decay curve.

The lipolysis index was greater in the two obese women groups compared with the normal weight and preobese groups (P<0.001).

Discussion

In this study, it is shown in normotriglyceridemic women with normal fasting plasma glucose that the FCR of the emulsion cholesteryl oleate correlates negatively with the BMI. There is no correlation between the FCR of the emulsion triglycerides and the BMI, but a positive correlation was found between the lipolysis index and BMI. Those results were obtained in women with a wide BMI range, spanning from 22 to 50 kg/m².

It is noteworthy that the triglyceride values were positively correlated with the BMI, whereas the HDL values correlated negatively with the BMI. Both increase in triglycerides and decrease in HDL levels are considered markers of insulin resistance,³¹ which implies that insulin resistance tends to increase as the BMI increases. This is important because the action of lipoprotein lipase is insulin dependent. Nonetheless, all participant subjects had normal fasting glucose levels and in the group of obese and morbid obese women, wherein the test was performed, the results of the oral glucose tolerance test were normal, except for just one woman in the morbid obese group. As a remark, HDL cholesterol values in the normal weight women group (1.26 mmol/l) could be considered somewhat low for the female sex at this age range.

Oral fat load tests are usually employed to evaluate post-prandial lipidemia status. In those tests, the ingestion of a standard fatty meal is followed by determination in sequential plasma samples of triglycerides and chylomicron labels such as retinyl palmitate¹² and apo B48.¹¹ In some studies, those determinations are made after plasma ultracentrifugation to separate the 'chylomicron' from 'nonchylomicron' fractions.³² However, the post-prandial lipidemia is made up of lipids of both intestinal and hepatic origin. Since both chylomicrons and VLDL undergo the same catabolic processes, both lipoproteins compete for lipoprotein lipase and thus VLDL also accumulates in the plasma in the post-prandial period.³³ Owing to this and other factors, such as the long period of fat intestinal absorption, the great interindividual variation in absorption rates and the short (10 min) half-lives of chylomicrons and remnants of the oral fat load test are difficult to interpret and may not be specific for chylomicron catabolism. In this regard, substantial amounts of apo B48, which is the apo B form present in chylomicrons, are found in the 'nonchylomicron' fraction and, conversely, apo B100, which is the VLDL apo B form, is found in the 'chylomicron' fraction.

The chylomicron-like emulsion method used in this study specifically tests the chylomicron metabolic pathway. In the plasma, the emulsions gain apolipoproteins from the circulating lipoproteins. The acquired apo CII stimulates lipoprotein lipase and apo E allows binding to the cell receptors that remove remnants from the plasma, similar to chylomicron metabolism. The emulsion shows plasma half-lives of cholesteryl esters and triglycerides that are equivalent to those of lymph chylomicrons in rats and subjects.^{17, 25} Since only minimal amounts of cholesteryl esters shift from the emulsion particles, this moiety is indeed a marker of the removal of the remnant particles.^{17, 25} Since the emulsions are injected intravenously, the gastrointestinal component is bypassed allowing straightforward calculation of the plasma kinetic data. Injected in minimal lipid amounts after a 12 h fasting, the emulsion does not disturb the VLDL metabolism. The injection into subjects of the double-labeled emulsion after the intake of the fatty meal resulted in diminution of the lipolysis index.²² In fact, the absorption of the meal lipids had a greater impact on the plasma clearance of the emulsion triglycerides than on the cholesterol ester clearance. In the fed subjects, there was a six-fold post-prandial decrease in the FCR of triglycerides, while the cholesteryl ester FCR was reduced by two-fold. Therefore, when challenged by the massive entry of chylomicron lipids into the circulation, the lipoprotein lipase function appears more readily saturable than the hepatic receptors that take up remnants.

In fat load tests, Couillard et al^{34, 35} and Guerci et al³² reported that obese subjects with normal fasting triglycerides display the AUC of post-prandial triglycerides of the 'chylomicron fraction' similar to the nonobese controls and accumulation of triglycerides of the nonchylomicron fraction, suggesting that VLDL triglycerides, and not those of chylomicrons, accumulate in plasma of the obese after a fatty meal. Jensen et al³⁶ and Mekki et al³⁷ found increased triglyceride AUC in the chylomicron fraction, but in both studies the obese had higher fasting triglycerides than their controls. In our previous study,⁹ the emulsion triglycerides were normally removed in normotriglyceridemic obese women and the lipolysis index was increased.

The finding in this study that the lipolysis index increases as the BMI increases does not necessarily imply that the activity of lipoprotein lipase is increased. As the clearance of the emulsion particles, expressed by the cholesteryl ester FCR, is inversely correlated with BMI, whereas the triglyceride FCR is unchanged, it can be assumed that the lipolysis of the particles continues for longer periods as the particles remain longer in the circulation than in normal weight subjects. Consequently, less triglycerides are removed by the liver together with the emulsion remnant particles and greater amounts are degraded by lipoprotein lipase. This results in increase in the lipolysis index that is calculated from the differences between the areas under the decay curves of the emulsion-labeled cholesteryl oleate and triglycerides. In this condition, remnants more depleted in triglycerides, conceivably of smaller size that offers greater potential for entry in the artery wall, and remaining in the blood stream for longer periods can become more atherogenic.³⁸ Regarding the activity of the enzyme, as measured in vitro in post-heparin plasma in obese vs nonobese subjects, the results from the literature are somewhat controversial. Some authors found alterations in the lipoprotein lipase activity in the obese,^{39, 40, 41, 42} whereas others did not^{11, 43, 44} and this may be related to several variables such as type of obesity, the plasma triglyceride levels and alterations in the insulin action.⁴⁵

Most studies found decreased removal of remnants in obesity, as evaluated by the B48^{11, 37} or retinyl palmitate^{12, 34, 35} measurement in the plasma after a test fatty meal or by chylomicron-like emulsion tests.^{9, 10, 46} However, Vansant et al⁴⁷ and Lewis et al¹² did not find obese vs control differences in retinyl palmitate AUC. Fat accumulation in visceral region, which is frequently associated to insulin resistance, has also been associated to decreased chylomicron remnant removal from circulation.^{10, 37, 47, 48} The decrease in remnant removal from the plasma may be consequent to the greater VLDL production by the liver in the obese, leading to competition between both lipoprotein classes and saturation of the removal mechanisms (Riches et al.^{11, 49} Increase in the VLDL hepatic production is consequent to the greater caloric intake by the obese.

Efficiency in the lipolysis process is a precondition for efficient removal of remnants from the circulation and it is expected that when the emulsion and for extension the chylomicron lipolysis is impaired, the plasma clearance of the particles is diminished.¹⁵ However, this is not the case of our study subjects, since the emulsion triglyceride FCR did not correlate with BMI and the lipolysis index was even increased as BMI increased. The negative correlation between remnant removal, expressed by the emulsion cholesteryl oleate, and the BMI of the study subjects found here can be ascribed to decrease in the function of the mechanisms that remove remnants. In this regard, Mamo¹¹ found decreased uptake of LDL by mononuclear cells of obese subjects, indicating reduction in the expression of the LDL receptors. LDL receptors in the liver are a major mechanism for remnant removal.^{15, 50}

Since apo E is the ligand for the remnants of the chylomicron-like emulsion to the receptor mechanisms that remove them from the circulation, it would be expected that the apo E isoforms might influence the emulsion clearance.^{51, 52} Apo E4/4 tends to increase remnant removal, whereas in the case of apo E2/2, the removal is the slowest. However, the frequency in the population of apo E4 and mainly E2 in the homozygous form, which is less than 1%, is too low to influence the results, as we documented in our previous study.²⁸

In concluding, in obesity the capacity to break down the chylomicron-like emulsion triglycerides is preserved and the lipolysis even increases as the BMI increases. However, the ability of the organism to remove remnants formed during this process decreases proportionally to the increase in BMI. Previously, it was shown that decreased removal of emulsion remnants¹⁷ or chylomicron markers in oral fat load tests^{38, 53, 54} is associated with CAD. Therefore, our results imply that remnant retention may be an important link between weight gain and atherogenesis.

References

1. Denke MA, Sempos CT, Grundy SM. Excess body weight: an under-recognized contributor to dyslipidemia in white American women. Arch Intern Med 1994; 154: 401–410. | Article | PubMed | ISI | ChemPort |
2. Lamon-Fava S, Wilson PWF, Schaefer EJ. Impact of body mass index on coronary heart disease risk factors in men and women. Arteriosclerosis Thromb Vasc Biol 1996; 16: 1509–1515.
3. Foster CJ, Weinsier RL, Birch R, Norris DJ, Bernstein RS, Wang J, Pierson RN, Van Itallie TB. Obesity and serum lipids: an evaluation of the relative contribution of body fat and fat distribution to lipid levels. Int J Obes 1987; 11: 151–161. | PubMed |
4. Mahaney MC, Blangero J, Comuzzie AG, VandeBerg JL, Stern MP, MacCluer JW. Plasma HDL cholesterol, triglyceride, and adiposity—a quantitative genetic test of conjoint trait Hipotesis in the San Antonio Family Heart Study. Circulation 1995; 92: 3240–3248. | PubMed | ISI | ChemPort |
5. Arai T, Yamashita S, Hirando K, Sakai N, Kotani K, Fujioka S, Nozaki K, Yamane M, Shinohara AHM, Islam W, Ishigami M, Nakamura T, Kameda-Takemura K, Tokunaga K, Matsuzawa Y. Increased plasma cholesterol ester transfer protein in obese subjects—a possible mechanism for the reduction of serum HDL cholesterol levels in obesity. Arteriosclerosis Thrombus 1994; 14: 1229–1236.
6. Connelly PW, Maguire GF, Lee M, Little JA. Plasma lipoproteins in familial hepatic lepase deficency. Arteriosclerosis 1990; 10: 40–48. | PubMed |
7. Perret B, Mabile L, Martinez L, Tercé F, Barbaras R, Collet X. Hepatic lipase: struture/function relationsship, synthesis and regulation. J Lipid Res 2002; 43: 1163–1169. | PubMed |
8. Seidell JC, Cigolini M, Charzewska J, Ellsinger B, Dibiase G. Fat distribution in European women: a comparison of anthropometrics measurements in relation to cardiovascular risk factors. Int J Epidemiol 1990; 19: 303–308. | PubMed |
9. Oliveira MRM, Maranhão RC. Plasma kinetics of a chylomicron-like emulsion in normolipidemic obese women after a short-period weight loss by energy-restricted diet. Metabolism 2002; 51: 1097–1103. | Article | PubMed |
10. Chan DC, Watts GF, Barrett PH, Mamo JCL, Redgrave RG. Markers of triglyceride-rich lipoprotein remnant metabolism in visceral obesity. Clin Chem 2002; 48: 278–283. | PubMed |
11. Mamo JCL, Watts GF, Barrett PHR, Smith D, James AP, Pal S. Post-prandial dyslipidemia in men with visceral obesity: an affect of reduced LDL receptor expression? Am J Physiol Endocrinal Metab 2001; 281: E626–E632.
12. Lewis GF, O'meara NM, Soltys PA, Blackman JD, Iverius PH, Druetzler AF, Getz GS, Polonsky KS. Post-prandial lipoprotein metabolism in normal and obese subjects: comparison after the vitamin A fat-loading test. J Clin Endocrinal Metab 1990; 71: 1041–1050.
13. Goldberg IJ. Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. J Lipid Res 1996; 37: 693–707. | PubMed | ISI | ChemPort |
14. Hussain MM, Kancha RK, Zhou Z, Luchoomun J, Zu H, Bakillah A. Chylomicron assembly and catabolism: role of apoliproteins and receptors. Biochim Biophys Acta 1996; 1300: 151–170. | PubMed | ISI | ChemPort |
15. Cooper AD. Hepatic uptake of chylomicron remnants. J Lipid Res 1997; 38: 2173–2192. | PubMed | ChemPort |
16. Linton MF, Hasty AH, Babaev VR, Fazio S. Hepatic apo E expression is required for remnant lipoprotein clearance in the absence of the low density lipoprotein receptor. J Clin Invest 1998; 101: 1726–1736. | PubMed | ISI | ChemPort |
17. Maranhão RC, Feres MC, Martins MT, Mesquita CH, Toffoletto O, Vinagre CGC, Gianini SD, Pileggi F. Plasma kinetics of a chylomicron-like emulsion in patients with coronary artery disease. Arteriosclerosis 1996; 126: 15–25.
18. Bernardes-Silva H, Toffoletto O, Bortolotto LA, Latrilha MC, Krieger EM, Pileggi F, Maranhão RC. Malignant hypertension is accompanied by marked alterations in chylomicron metabolism. Hypertension 1995; 26: 1207–1210. | PubMed |
19. Sakashita AM, Bydlowski SP, Chamone DAF, Maranhão RC. Plasma kinetics of an artificial emulsion resembling chylomicrons in patients with chronic lymphocyte leukemia. Ann Hematol 2000; 79: 687–690. | Article | PubMed |
20. Vinagre CG, Stolf NAG, Bocchi E, Maranhão RC. Chylomicron metabolism in patients submitted to cardiac transplantation. Transplantation 2000; 69: 532–537. | Article | PubMed |
21. Santos RD, Sposito AC, Ventura LI, Cesar LAM, Ramires JAF, Maranhão RC. Effect of prevastatin on plasma removal of a chylomicron-like emulsion in men with coronary artery disease. Am J Cardiol 2000; 85: 1163–1166. | Article | PubMed |
22. Maranhão RC, Roland IA, Hirata MH. Effects of Triton WR 1339 and heparin on transfer of surface lipids from triglyceride-rich emulsions to high-density lipoproteins in rats. Lipids 1990; 25: 701–705. | PubMed |
23. Redgrave TG, Roberts DCK, West CE. Separation of plasma lipoprotein by density-gradient ultra centrifugation. Anal Biochem 1975; 65: 42–49. | Article | PubMed | ChemPort |
24. Smith EM. Dose estimate techniques. In: Rollo FD (ed). Nuclear medicine physics, instrumentation and agents. Mosby: Saint Louis, USA; 1977.
25. Redgrave TG, Ly HL, Quintão ECR, Ramberg CF, Boston RC. Clearance from plasma of triacylglycerol and cholesteryl ester after intravenous injection of chylomicron-like emulsions in rats and man. Biochem J 1993; 290: 843–847. | PubMed |
26. Redgrave TG, Zeck LA. A kinetic model of chylomicron core lipid metabolism in rats: the effect of single meal. J Lipid Res 1987; 5: 473–482.
27. Marchese SRM, Mesquita CH, Cunha IIL. Anacomp program application to calculate ¹³⁷C transfer rates in marine organisms and dose in man. J Radioanal Nucl Chem 1998; 232: 233–236.
28. Santos RD, Ventura LI, Spósito AC, Schreiber R, Ramires JAF, Maranhão RC. The effects of gemfibrozil upon the metabolism of chylomicron-like emulsions in patients with endogenous hypertriglyceridemia. Cardiovasc Res 2001; 49: 456–465. | Article | PubMed |
29. Friedewald WT, Levy RI, Fredrickson DD. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502. | PubMed | ISI | ChemPort |
30. American Diabetes Association. Clinical practice recommendations: screening for type 2 diabetes. Diabetes Care 2000; 23 (Suppl): S20–S23. | PubMed | ISI |
31. Frayn KN. Adipose tissue and the insulin resistance syndrome. Proc Nutr Soc 2001; 60: 375–380. | PubMed |
32. Guerci B, Vergès B, Durlach V, Hadjadj S, Drouin P, Paul J-L. Relationship between altered post-prandil lipemia and insulin resistance in normolipidemic and normoglucose tolerant obese patients. Intern J Obes Relat Metab Disord 2000; 24: 468–478. | Article |
33. Björkegren J, Packard CJ, Hamsten A, Bedford D, Caslake M, Foster L, Shepherd J, Stwart P, Karpe F. Accumulation of large very low density lipoprotein in plasma during intravenous infusion of a chylomicron-like triglyceride emulsion reflects competition for a common lipolytic pathway. J Lipid Res 1996; 37: 79–86.
34. Couillard C, Bergeron N, Prud'homme D, Bergeron J, Tremblay A, Bouchard C, Mauriège P, Després JP. Post-prandial triglyceride response in visceral obesity in men. Diabetes 1998; 47: 953–960. | Article | PubMed | ISI | ChemPort |
35. Couillard C, Berberon N, Beregron J, Pascot A, Mauriège P, Tremblay A, Prud'homme D, Bouchard C, Després J-P. Metabolic heterogeneity underlying post-prandil lipemia among men with low fasting high-density lipoprotein cholesterol concentrations. J Clin Endocrinal Metabol 2000; 85: 4575–4582. | Article |
36. Jensen J, Bysted A, Dawids S, Hermansen K, Holmer G. The effect of palm oil, lard, and puff pastry margarine on post-prandial lipid and hormone responses in normal-weight and obese young women. Br J Nutr 1999; 82: 469–479. | PubMed | ChemPort |
37. Mekki N, Christofilis MA, Charbonnier M, Atlan-gepner C, Defoort C, Juhel C, Borel P, Portugal H, Pauli AM, Vialettes B, Lairon D. Influence of obesity and body fat distribution on post-prandial lipemia and triglyceride-rich lipoprotein in adult women. J Clin Endocrinal Metab 1999; 84: 184–191. | Article |
38. Karpe F, Steiner G, Uffelman K, Olivecrona T, Hamsten A. Postprandial lipoproteins and progression of coronary atheroscleroses. Atheroscleroses 1994; 106: 83–97.
39. Kobayashi J, Saito K, Fukamachi I, Taira K, Takahashi K, Bujo H, Saito Y. Pre-heparin plasma lipoprotein lipase mass: correlation with intra-abdominal visceral fat accumulation. Horm Metab Res 2001; 33: 412–416. | Article | PubMed |
40. Kin JK, Fillmore JJ, Chen Y, Yu C, Moore IK, Pypaert M, Lutz EP, Kako Y, Velez-Carrasco W, Goldberg IJ, Breslow JL, Shulman GI. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci USA 2001; 98: 7522–7527. | Article | PubMed | ChemPort |
41. Ranganath LR, Beety JM, Wright J, Margan LM. Nutrient regulation of post-heparin lipoprotein lipase activity in obese subjects. Horm Metab Res 2001; 33: 57–61. | Article | PubMed |
42. Maheux P, Azhar S, Kern PA, Chen YD, Reuven GM. Relationship between insulin-mediated glucose disposal and regulation of plasma and adipose tissue lipoprotein lipase. Diabetologia 1997; 40: 850–858. | Article | PubMed |
43. Panarotto D, Rémillard P, Bouffard L, Maheux P. Insulin resistance affects the regulation of lipoprotein lipase in the postprandial period and in an adipose tissue-specific manner. Eur J Clin Invest 2002; 32: 84–92. | Article | PubMed | ChemPort |
44. Pykälisto OJ, Smith PH, Brunzell JD. Determinant of human adipose tissue lipoprotein lipase. J Clin Inv 1975; 56: 1108–1117.
45. Frayn KN. Adipose tissue as a buffer for daily lipid flux. Diabetologia 2002; 45: 1201–1210. | Article | PubMed | ISI | ChemPort |
46. Watts GF, Chan DCF, Barrett PHR, Martins IJ, Redgrave TG. Preliminary experience with a new stable isotope breath test for chylomicron remnant metabolism: a study in central obesity. Clin Sci 2001; 101: 683–690. | Article | PubMed |
47. Vansant G, Mertens A, Muls E. Determinants of post-prandial lipemia in obese women. Intern J Obes Relat Metabolic Disord 1999; 23 (Suppl): 14–21. | Article |
48. Taira M, Hikita M, Kobayashi J, Bujo H, Takahashi K, Murano S, Morisaki N, Saito Y. Delayed post-prandial lipid metabolism in subjects with intra-abdominal visceral fat accumulation. Eur J Clin Inv 1999; 29: 301–308. | Article |
49. Riches FM, Watts GF, Naoumova RP, Kelly JM, Croft KD, Thompson GR. Hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 studied with a stable isotope technique in men with visceral obesity. Int J Obes Relat Metabolic Disord 1998; 22: 414–423. | Article |
50. Mahley RW. Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apoliprotein E. J Lipid Res 1999; 40: 1–16. | PubMed | ISI | ChemPort |
51. Brenninkmeijer BJ, Stuyt PMJ, Demacker PMN, Stalenhoef AFH, Laar A. Catabolism of chylomicron remnants in normolipidemic subjects in relation to the apoprotein E phenotype. J lipid Res 1987; 28: 361–370. | PubMed |
52. Weintraub MS, Eisenberg S, Breslow JL. Dietary fat clearance in normal subjects is regulated by genetic variation in apolipoprotein E. J Clin Invest 1987; 80: 1571–1577. | PubMed | ChemPort |
53. Simons LA, Dwyer T, Simons J, Bernstein L, Mock P, Poonia NS, Balasubramaniam S, Baron D, Branson J, Morgan J, Roy P. Chylomicrons and Chylomicron remnants in coronary artery disease: a case–control study. Atherosclerosis 1987; 65: 181–189. | Article | PubMed | ChemPort |
54. Groot PHE, Stiphout WAHJV, Kraus XH, Jansen H, Tol AV, Ramshorst EV, Chin-On S, Hofman A, Cresswell SR, Havekes L. Postprandial lipoprotein metabolism in normolipidemic men with and without coronary artery disease. Arter Thromb 1991; 11: 653–662.

Acknowledgements

This study was supported by the State of São Paulo Research Support Foundation (FAPESP), São Paulo, Brazil. Dr Oliveira had a scholarship from FAPESP and Dr Maranhão holds a Research Award from the National Council of Scientific and Technological Development (CNPq), Brasilia, Brazil.