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Increased plasma apoA-IV level is a marker of abnormal postprandial lipemia: a study in normoponderal and obese subjects

2001; Elsevier BV; Volume: 42; Issue: 12 Linguagem: Inglês

10.1016/s0022-2275(20)31531-5

ISSN

1539-7262

Autores

Bruno Vergès, Bruno Guerci, Vincent Durlach, Catherine Galland-Jos, Jean Paul, Laurent Lagrost, Philippe Gambert,

Tópico(s)

Cancer, Lipids, and Metabolism

Resumo

Plasma apolipoprotein A-IV (apoA-IV) levels are found elevated in hypertriglyceridemic patients. However, the relationship between plasma apoA-IV level and postprandial lipemia is not well known and remains to be elucidated. Thus, our objective was to study the relationship between plasma apoA-IV and postprandial TG after an oral fat load test (OFLT). Plasma apoA-IV was measured at fast and during an OFLT in 16 normotriglyceridemic, normoglucose-tolerant android obese subjects (BMI = 34.6 ± 2.9 kg/m2) and 30 normal weight controls (BMI = 22.2 ± 2.3 kg/m2). In spite of not statistically different fasting plasma TG levels in controls and obese patients, the former group showed an altered TG response after OFLT, featuring increased nonchylomicron TG area under the curve (AUC) compared with controls (516 ± 138 vs. 426 ± 119 mmol/l·min, P < 0.05). As compared to controls, obese patients showed increased apoA-IV levels both at fast (138.5 ± 22.4 vs. 124.0 ± 22.8 mg/l, P < 0.05) and during the OFLT (apoA-IV AUC: 79,833 ± 14,281 vs. 68,176 ± 17,463 mg/l·min, P < 0.05). Among the whole population studied, as among the control and obese subgroups, fasting plasma apoA-IV correlated significantly with AUC of plasma TG (r = 0.60, P = 0.001), AUC of chymomicron TG (r = 0.45, P < 0.01), and AUC of nonchylomicron TG (r = 0.62, P < 0.001). In the multivariate analysis, fasting apoA-IV level constituted an independent and highly significant determinant of AUC of plasma TG, AUC of chymomicron TG, AUC of nonchylomicron TG, and incremental AUC of plasma TG. In conclusion, we show a strong link between fasting apoA-IV and postprandial TG metabolism. Plasma fasting apoA-IV is shown to be a good marker of TG response after an OFLT, providing additional information on post-load TG response in conjunction with other known factors such as fasting TGs.—Vergès, B., B. Guerci, V. Durlach, C. Galland-Jos, J. L. Paul, L. Lagrost, and P. Gambert. Increased plasma apoA-IV level is a marker of abnormal postprandial lipemia: a study in normoponderal and obese subjects. J. Lipid Res. 2001. 42: 2021–2029. Plasma apolipoprotein A-IV (apoA-IV) levels are found elevated in hypertriglyceridemic patients. However, the relationship between plasma apoA-IV level and postprandial lipemia is not well known and remains to be elucidated. Thus, our objective was to study the relationship between plasma apoA-IV and postprandial TG after an oral fat load test (OFLT). Plasma apoA-IV was measured at fast and during an OFLT in 16 normotriglyceridemic, normoglucose-tolerant android obese subjects (BMI = 34.6 ± 2.9 kg/m2) and 30 normal weight controls (BMI = 22.2 ± 2.3 kg/m2). In spite of not statistically different fasting plasma TG levels in controls and obese patients, the former group showed an altered TG response after OFLT, featuring increased nonchylomicron TG area under the curve (AUC) compared with controls (516 ± 138 vs. 426 ± 119 mmol/l·min, P < 0.05). As compared to controls, obese patients showed increased apoA-IV levels both at fast (138.5 ± 22.4 vs. 124.0 ± 22.8 mg/l, P < 0.05) and during the OFLT (apoA-IV AUC: 79,833 ± 14,281 vs. 68,176 ± 17,463 mg/l·min, P < 0.05). Among the whole population studied, as among the control and obese subgroups, fasting plasma apoA-IV correlated significantly with AUC of plasma TG (r = 0.60, P = 0.001), AUC of chymomicron TG (r = 0.45, P < 0.01), and AUC of nonchylomicron TG (r = 0.62, P < 0.001). In the multivariate analysis, fasting apoA-IV level constituted an independent and highly significant determinant of AUC of plasma TG, AUC of chymomicron TG, AUC of nonchylomicron TG, and incremental AUC of plasma TG. In conclusion, we show a strong link between fasting apoA-IV and postprandial TG metabolism. Plasma fasting apoA-IV is shown to be a good marker of TG response after an OFLT, providing additional information on post-load TG response in conjunction with other known factors such as fasting TGs. —Vergès, B., B. Guerci, V. Durlach, C. Galland-Jos, J. L. Paul, L. Lagrost, and P. Gambert. Increased plasma apoA-IV level is a marker of abnormal postprandial lipemia: a study in normoponderal and obese subjects. J. Lipid Res. 2001. 42: 2021–2029. Human apolipoprotein A-IV (apoA-IV) is a 46-kDa plasma apolipoprotein that is synthesized predominantly in the small intestine (1Utermann G. Beisiegel V. Apolipoprotein A-IV: a protein occurring in human mesenteric lymph chylomicrons and free in plasma: isolation and quantification.Eur. J. Biochem. 1979; 99: 333-343Google Scholar, 2Green P.H. Glickman R.M. Saudek C.D. Blum C.B. Tall A.R. Human intestinal lipoproteins: studies in chyluric subjects.J. Clin. Invest. 1979; 64: 233-242Google Scholar, 3Green P.H. Glickman R.M. Riley J.W. Quinet E. Human apolipoprotein A-IV: intestinal origin and distribution in plasma.J. Clin. Invest. 1980; 65: 911-919Google Scholar, 4Weinberg R.B. Scanu A.M. Isolation and characterisation of human apolipoprotein A-IV from lipoprotein depleted serum.J. Lipid. Res. 1983; 24: 52-59Google Scholar). ApoA-IV is found to be associated in plasma with TG-rich lipoproteins and HDL particles (5Lagrost L. Gambert P. Boquillon M. Lallemant C. Evidence for high density lipoproteins as the major apolipoprotein A-IV-containing fraction in normal human serum.J. Lipid. Res. 1989; 30: 1525-1534Google Scholar). Although its precise function remains unclear, apoA-IV has been proposed to play a role in the metabolism of both TG-rich lipoproteins and HDL. ApoA-IV has been shown to modulate the activation of lipoprotein lipase in the presence of apoC-II (6Goldberg I.J. Scheraldi C.A. Yacoub L.X. Saxena U. Bisgaier C.L. Lipoprotein Apo C II activation of lipoprotein lipase. Modulation by apolipoprotein A-IV.J. Biol. Chem. 1990; 265: 4266-4272Google Scholar). ApoA-IV is thought to play a potentially important role in reverse cholesterol transport because it has been shown to stimulate lecithin: cholesterol acyl transferase (LCAT) activity (7Steinmetz A. Utermann G. Activation of lecithin: cholesterol acyl transferase by human apolipoprotein A-IV.J. Biol. Chem. 1985; 260: 2258-2264Google Scholar, 8Chen C.H. Albers J.J. Activation of lecithin: cholesterol acyl transferase by apolipoproteins E-2, E-3 and A-IV isolated from human plasma.Biochim. Biophys. Acta. 1985; 836: 279-285Google Scholar), to bind to bovine aortic endothelial cells (9Savion N. Gamliel A. Binding of apolipoprotein A-I and apolipoprotein A-IV to cultured bovine aortic endothelial cells.Arteriosclerosis. 1988; 8: 178-186Google Scholar) and to hepatic tissue (10Dvorin E. Gorder N.L. Benson D.M. Gotto Jr., A. Apolipoprotein A-IV. A determinant for binding and uptake of high density lipoproteins by rat hepatocytes.J. Biol. Chem. 1986; 261: 15714-15718Google Scholar, 11Weinberg R.B. Patton C.S. Binding of human apolipoprotein A-IV to human hepatocellular plasma membranes.Biochim. Biophys. Acta. 1990; 1044: 255-261Google Scholar), to stimulate cholesterol efflux from adipose cells (12Stein O. Stein Y. Lefevre M. Roheim P.S. The role of apolipoprotein A-IV in reverse cholesterol transport studied with cultured cells and liposomes derived from another analog of phosphatidylcholine.Biochim. Biophys. Acta. 1986; 878: 7-13Google Scholar, 13Steinmetz A. Barbaras R. Ghalim N. Clavey V. Fruchart J.C. Ailhaud G. Human apolipoprotein A-IV binds to apolipoprotein AI/AII receptor sites and promotes cholesterol efflux from adipose cells.J. Biol. Chem. 1990; 265: 7859-7863Google Scholar), and to participate in HDL particle conversion by cholesteryl ester transfer protein (CETP) (14Barter P.J. Rajaram O.U. Chang L.B. Rye K.A. Gambert P. Lagrost L. Ehnholm C. Fidge N.H. Isolation of a high density lipoprotein conversion factor from human plasma. A possible role of apolipoprotein A-IV as its activator.Biochem J. 1988; 254: 179-184Google Scholar, 15Lagrost L. Gambert P. Dangremont V. Athias A. Lallemant C. Role of cholesteryl ester transfer protein (CETP) in the HDL conversion process as evidenced by using anti-CETP monoclonal antibodies.J. Lipid Res. 1990; 31: 1569-1575Google Scholar). ApoA-IV can modulate CETP-mediated transfer of cholesteryl esters between HDL and LDL fractions (16Guyard-Dangremont V. Lagrost L. Gambert P. Comparative effects of purified apolipoproteins A-I, A-II and A-IV on cholesteryl ester transfer protein activity.J. Lipid Res. 1994; 35: 982-992Google Scholar). Moreover, Weinberg, Ibdah, and Phillips (17Weinberg R.B. Ibdah J.A. Phillips M.C. Adsorption of apolipoprotein A-IV to phospholipid monolayers spread at the air/water interface: a model for its labile binding to high density lipoproteins.J. Biol. Chem. 1992; 267: 8977-8983Google Scholar) demonstrated that apoA-IV exhibits labile reversible binding to HDL3 and proposed that apoA-IV helps to maintain optimal surface pressure for CETP activity. Furthermore, apoA-IV could be a signal for satiety in the central nervous system (18Fujimoto K. Cardelli J.A. Tso P. Increased apolipoprotein A-IV in rat mesenteric lymph after lipid meal acts as a physiological signal for satiation.Am. J. Physiol. 1992; 262: G1002-G1006Google Scholar, 19Merril Jr., A.H. ApoA-IV: a new satiety signal.Nutrition Reviews. 1993; 51: 273-275Google Scholar). For several years, postprandial lipid metabolism has received considerable attention because it has been shown that postprandial TG-rich lipoproteins are involved in the development of atherosclerosis (20Zilversmit D.B. Atherogenesis: a postprandial phenomenon.Circulation. 1979; 60: 473-485Google Scholar, 21Miesenbock G. Patsch J.R. Postprandial hyperlipidemia: the search for atherogenic lipoprotein.Curr. Opin. Lipid. 1992; 3: 196-201Google Scholar). Many studies comparing patients with coronary heart disease and controls have demonstrated differences in postprandial TG after an oral fat load test (OFLT) (22Nikkila M. Solakivi T. Lehtimaki T. Koivula T. Laippala P. Astrom B. Postprandial plasma lipoprotein changes in relation to apolipoprotein E phenotypes and low density lipoprotein size in men with and without coronary artery disease.Atherosclerosis. 1994; 106: 149-157Google Scholar, 23Groot P.H.E. Van Stiphout W.A.H. Krauss X.H. Jansen H. Van Tol A. Van Ramshorst E. Chin-On S. Hofman A. Cresswell S.R. Havekes L. Postprandial lipoprotein metabolism in normolipidemic men with and without coronary artery disease.Arterioscler. Thromb. 1991; 11: 653-662Google Scholar) and shown that postprandial TG level was an independent predictor of coronary artery disease in multivariate analysis (24Patsch J.R. Miesenböck G. Hopferwieser T. Mühlberger V. Knapp E. Dunn J.K. Gotto A.M. Patsch W. Relation of triglyceride metabolism and coronary artery disease.Arterioscler. Thromb. 1992; 12: 1336-1345Google Scholar, 25Weintraub M.S. Grosskopf I. Rassin T. Miller H. Charach G. Rotmensch H.H. Liron M. Rubinstein A. Iaina A. Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years.BMJ. 1996; 312: 935-939Google Scholar). Others and we have reported altered postprandial lipemia in obese subjects (26Lewis G.F. O'Meara N.M. Soltys P.A. Blackman J.D. Iverius P.H. Druetzler A.F. Getz G.S. Polonsky K.S. Postprandial lipoprotein metabolism in normal and obese subjects: comparison after the vitamin A fat-loading test.J. Clin. Endocrinol. Metab. 1990; 71: 1041-1050Google Scholar, 27Couillard C. Bergeron N. Prudw'homme D. Bergeron J. Tremblay A. Bouchard C. Mauriège P. Després J.P. Postprandial triglyceride response in visceral obesity in men.Diabetes. 1998; 47: 953-960Google Scholar, 28Guerci B. Vergwès B. Durlach V. Hadjadj S. Drouin P. Paul J.L. Relationship between altered postprandial lipemia and insulin resistance in normolipidemic and normoglucose tolerant obese patients.Int. J. Obes. 2000; 24: 468-478Google Scholar), which could explain, at least partly, the greater development of cardiovascular disease in the obese population. Several studies have pointed out a link between apoA-IV and TG metabolism. Indeed, plasma apoA-IV levels are found elevated in hypertriglyceridemic patients (29Lagrost L. Gambert P. Meunier S. Morgado P. Desgres J. d'Athis P. Lallemant C. Correlation between apolipoprotein A-IV and triglyceride concentrations in human sera.J. Lipid Res. 1989; 30: 701-710Google Scholar, 30Vergès B. Vaillant G. Goux A. Lagrost L. Brun J.M. Gambert P. Apolipoprotein A-IV levels and phenotype distribution in non insulin dependent diabetes mellitus.Diabetes Care. 1994; 17: 810-817Google Scholar, 31Vergès B. Rader D. Schaeffer J. Zech L. Kindt M. Fairwell T. Gambert P. Brewer Jr., H.B. In vivo metabolism of apolipoprotein A-IV in severe hypertriglyceridemia: a combined radiotracer and stable isotope kinetic study.J. Lipid Res. 1994; 35: 2280-2291Google Scholar). We have previously shown that increased plasma apoA-IV levels associated with hypertriglyceridemia are due to delayed catabolism of apoA-IV (31Vergès B. Rader D. Schaeffer J. Zech L. Kindt M. Fairwell T. Gambert P. Brewer Jr., H.B. In vivo metabolism of apolipoprotein A-IV in severe hypertriglyceridemia: a combined radiotracer and stable isotope kinetic study.J. Lipid Res. 1994; 35: 2280-2291Google Scholar). However, very little is known about the relationship between plasma apoA-IV level and postprandial lipemia, and so far, only few studies performed in a limited number of normal subjects have been reported (3Green P.H. Glickman R.M. Riley J.W. Quinet E. Human apolipoprotein A-IV: intestinal origin and distribution in plasma.J. Clin. Invest. 1980; 65: 911-919Google Scholar, 32Bisgaier C.L. Sachdev O.P. Megna L. Glickman R.M. Distribution of apolipoprotein A-IV in human plasma.J. Lipid Res. 1985; 26: 11-25Google Scholar, 33Dallongeville J. Lebel P. Parra H.J. Luc G. Fruchart J.C. Postprandial lipaemia is associated with increased levels of apolipoprotein A-IV in triacylglycerol-rich fraction and decreased levels in the denser plasma fractions.Br. J. Nutr. 1997; 77: 213-223Google Scholar). Thus, to gain further insight into the relationship between apo-IV and postprandial lipid metabolism, we aimed to study the possible link between plasma apoA-IV and postprandial TG after an OFLT in normolipidemic obese subjects with altered post-fat load TG responses and in normal weight healthy controls. A group of 30 normal weight controls (17 men, 13 women) and 16 obese patients (5 men, 11 women) were recruited. All had a normal glucose tolerance (fasting plasma glucose <6.1 mmol/l and 2-h plasma glucose 0.90 mmol/l for men and 1.03 mmol/l for women, and LDL cholesterol 30 kg/m2; 2) abdominal (android) fat distribution, defined by a waist-to-hip ratio >0.85 for women and >0.95 for men; 3) none of the patients was morbidly obese. Healthy subjects were selected according to the following criteria: BMI 18–25 kg/m2 and stable body weight (<2% change in the last 3 months). All the subjects (obese and control) had no symptoms of illness, no family history of premature coronary disease (before 60 years), and normal values for blood creatinine, sodium, potassium, chloride, total protein, total and direct bilirubin, activities of aspartate (AST) or alanine (ALT) amino-transferase, and gamma-glutamyl transferase (ΓGT). None had any endocrine or gastrointestinal disease, hypertension (systolic blood pressure <140 mmHg, diastolic blood pressure 10 cigarettes daily for at least 5 years). None of the participants (obese or controls) were on any medication known to affect carbohydrate or lipoprotein metabolism, and their alcohol intake was limited (<20 g/day). All the women were premenopausal (in follicular cycle) and none was taking oral contraceptive or hormone replacement therapy. This project was approved by the local Ethics committee of the Nancy University Hospital (France), and all subjects gave their written informed consent. A weight maintenance diet was prescribed for all subjects [50% carbohydrate, 33% fat (polyunsaturated/saturated ratio 80%) and 17% protein] for the 7 days before the study to ensure uniformity. Three days before the OFLT, subjects were instructed to maintain their usual level of activity and to refrain from any strenuous exercise to limit the influence of acute exercise, which alters lipid metabolism (34Aldred H.E. Perry I.C. Hardman A.E. The effect of a single bout of brisk walking on postprandial lipemia in normolipidemic young adults.Metabolism. 1994; 43: 836-841Google Scholar, 35Foger B. Patsch J.R. Exercise and postprandial lipaemia.J. Cardiovasc. Risk. 1995; 2: 316-322Google Scholar). For the same reason, alcohol was not allowed during the 3 days immediately before OFLT (36Pownal H.J. Dietary ethanol is associated with reduced lipolysis of intestinally derived lipoproteins.J. Lipid Res. 1994; 35: 2105-2113Abstract Full Text PDF Google Scholar, 37Hartung G.H. Lawrence S.J. Reeves R.S. Foreyt J.P. Effect of alcohol and exercise on postprandial lipemia and triglyceride clearance in men.Atherosclerosis. 1993; 100: 33-40Google Scholar). Subjects remained fasted during the 12 h before the oral fat load was given (at 8:00 am). The OFLT was performed as previously reported (28Guerci B. Vergwès B. Durlach V. Hadjadj S. Drouin P. Paul J.L. Relationship between altered postprandial lipemia and insulin resistance in normolipidemic and normoglucose tolerant obese patients.Int. J. Obes. 2000; 24: 468-478Google Scholar). In summary, the fat load consisted of 180 g of a blended emulsified meal containing 88 mg cholesterol, 35 g saturated fatty acid, and 30 g mono- and 15 g polyunsaturated fatty acid (Laboratoires Pierre Fabre Santé, Castres, France). It provided 890 calories (85% fat, 13% carbohydrates, and 2% protein). The fat load was ingested in 15 min with 200 ml water. No further food or drink was allowed during the study period. The participants were instructed to remain in bed in a supine position. Plasma apoA-IV concentrations were measured using a competitive enzyme immunoassay standardized with purified apoA-IV, as previously described (29Lagrost L. Gambert P. Meunier S. Morgado P. Desgres J. d'Athis P. Lallemant C. Correlation between apolipoprotein A-IV and triglyceride concentrations in human sera.J. Lipid Res. 1989; 30: 701-710Google Scholar, 38Lagrost L. Gambert P. Boquillon M. Lallemant C. Evidence for high density lipoproteins as the major apolipoprotein A-IV containing fraction in normal human serum.J. Lipid Res. 1989; 30: 1525-1534Google Scholar). The coefficient of variability for this apoA-IV assay was 3.0% within runs and 3.9% between runs. ApoA-IV phenotyping was performed by isoelectric focusing of delipidated plasma samples and immunoblotting (39Menzel H.J. Boerwinkle E. Schrangl-Will S. Utermann G. Human apolipoprotein A-IV polymorphism: frequency and effect on lipid and lipoproteins levels.Hum. Genet. 1988; 79: 368-372Google Scholar). Total cholesterol and TG were measured enzymatically (bioMérieux, Marcy l'Etoile, France). HDL cholesterol was assessed by phosphotungstic acid precipitation, and LDL cholesterol was calculated according to the Friedewald formula (40Friedewald W.T. Levy R.I. Frederickson J. Estimation of the concentration of low-density cholesterol in plasma without the use of the preparative ultra-centrifuge.Clin. Chem. 1972; 18: 499-502Google Scholar). HDL2 and HDL3 cholesterol concentrations were determined by nondenaturating electrophoresis in discontinuous gradient gels (41Atger V. Malon D. Bertière M.C. N'Diaye F. Girard-Globa A. Cholesterol distribution between high-density-subfractions HDL2 and HDL3 determined in serum by discontinuous gradient gel electrophoresis.Clin. Chem. 1991; 37: 1149-1152Google Scholar). ApoA-I and apoB were determined by immunonephelometry with commercial kits (Beckman, Gagny, France). Plasma glucose was determined enzymatically (PAP 250; bioMérieux). Total plasma insulin concentration was measured by immunoenzymatic assay (Insulin IMX®; Abbott Laboratories, Tokyo, Japan). Cross reactivity with proinsulin was <0.05%. The apoE genotypes were determined using HhaI restriction enzyme and PCR (42Clavel C. Durlach A. Durlach V. Birembaut P. Rapid and safe determination of human apolipoprotein E genotypes by miniaturised SDS-PAGE in non-insulin dependent diabetes mellitus.J. Clin. Pathol. 1995; 48: 295-299Google Scholar). Fasting plasma leptin concentrations were measured in triplicate by radioimmunoassay (LINCO Research Inc., Saint-Louis, MO). The intra- and inter-assay coefficients of variation were 4.5 and 8%, respectively. Insulin sensitivity was assessed from blood samples collected 30, 20, and 10 minutes before the ingestion of the oral fat load using the homeostasis model assessment (HOMA) system described by Matthews et al. (43Matthews D.R. Hosker J.P. Rudenski A.S. Naylor B.A. Treacher D.F. Turner R.C. Homeostatis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man.Diabetologia. 1985; 28: 412-419Google Scholar) with the formula (insulin mU/l × plasma glucose mmol/l)/22.5. Blood samples were monitored as previously reported (28Guerci B. Vergwès B. Durlach V. Hadjadj S. Drouin P. Paul J.L. Relationship between altered postprandial lipemia and insulin resistance in normolipidemic and normoglucose tolerant obese patients.Int. J. Obes. 2000; 24: 468-478Google Scholar). In summary, blood samples were taken 30, 20, and 10 minutes before the fat load, at the time of the fat load, and 2, 3, 4, 5, 6, and 8 hours later (T0, T2, T3, T4, T5, T6, and T8). Plasma apoA-IV levels were measured at T0, T4, and T8. The apoE genotype, apoA-I and apoB, plasma total LDL and HDL cholesterol, and HDL2 and HDL3 cholesterol concentrations were determined at T0. The lipoprotein fraction (supernatant) containing chylomicrons was isolated by ultracentrifugation for 30 min at 25,000 rpm in a Beckman (Palo Alto, CA) XL-80 ultracentrifuge, rotor Ti-SW 41. The infranatant was collected and named the nonchylomicron fraction, which contained TG-rich lipoproteins (chylomicron remnants, VLDL, and VLDL remnants). Mean recovery (±SD) was 98 ± 3% for TG. TG in the plasma and fractions were assayed within the day. Data are means ± SD. The areas under the time concentration curves [area under the curves (AUCs)] were calculated by the trapezoidal method (44Matthews J.N.S. Altman D.G. Campbell M.J. Royton P. Analysis of serial measurements in medical research.BMJ. 1990; 300: 230-235Google Scholar). Incremental AUC (AUCi) was evaluated after subtracting the initial individual value (T0) from all respective postprandial measurements, yielding the net postprandial change. Means were compared between two groups by Student's unpaired t-test and between several groups by ANOVA. For paired data, means between two groups were compared with the paired t-test. Data were compared by the nonparametric Mann-Whitney U-test when men and women were analyzed separately. The χ2 test was used to compare frequencies between controls and obese subjects. When the distribution of a variable was not normal, as assessed by the Kolmogorov-Smirnov test, data were log-transformed for univariate and multivariate regression analyses. The correlation coefficients (r) were determined by linear regression analysis. Statistical significance of the correlation coefficients was determined by the method of Fisher and Yates (45Armitage P. Berry G. Statistical Methods in Medical Research. Blackwell Scientific Publications, Oxford, UK1971Google Scholar). Multiple linear regression analyses were performed to identify significant independent predictors of postprandial lipemia parameters and significant independent predictors of fasting plasma apoA-IV level. Significance was implied at P < 0.05. Statistical analyses were performed using the SPSS software (SPSS, Inc., Chicago, IL). The clinical and biological characteristics of the obese subjects and controls are shown in Table 1. Obese subjects had significantly higher BMI, waist-to hip ratio, HOMA, plasma glucose, insulin, and leptin levels than controls. For all characteristics listed in Table 1, there were no significant differences between men and women except for waist-to-hip ratio (higher in men than in women in both controls and obese subjects) and leptin levels (higher in women than in men in both controls and obese subjects) (data not shown).TABLE 1.Clinical and biological characteristics of the control and obese subjectsControls (n = 30)Obese Subjects (n = 16)Sex ratio (male/female)17/135/11aNot significant.Age (years)30.9 ± 8.941.3 ± 9.2bP < 0.001.BMI (kg/m2)22.2 ± 2.334.6 ± 2.9bP < 0.001.Waist/hip ratio0.82 ± 0.070.94 ± 0.06bP < 0.001.Fasting plasma glucose (mmol/l)4.76 ± 0.525.54 ± 0.64bP < 0.001.Fasting plasma insulin (pmol/l)31.3 ± 11.563.5 ± 26.2bP < 0.001.HOMA1.13 ± 0.492.65 ± 1.25bP < 0.001.Leptin (ng/ml)6.1 ± 5.127.5 ± 16.2bP < 0.001.Data are means ± SD. BMI, body mass index. HOMA, homeostasis model assessment.a Not significant.b P < 0.001. Open table in a new tab Data are means ± SD. BMI, body mass index. HOMA, homeostasis model assessment. Fasting lipid parameters in control and obese subjects are shown in Table 2. HDL cholesterol concentrations were lower in obese subjects compared with controls but remained within the normal range. HDL2 cholesterol levels was significantly lower in obese patients than in controls (P < 0.01). For all lipid values listed in Table 2, there were no significant differences between men and women except for HDL2 cholesterol levels (higher in women than in men in both controls and obese subjects) (data not shown).TABLE 2.Fasting lipid parameters of control and obese subjectsControls (n = 30)Obese Subjects (n = 16)Total cholesterol (mmol/l)4.33 ± 0.774.66 ± 0.74aNot significant.Fasting TG (mmol/l)0.77 ± 0.320.93 ± 0.23aNot significant.HDL cholesterol (mmol/l)1.24 ± 0.221.08 ± 0.27bP < 0.05.HDL2 cholesterol (mmol/l)0.48 ± 0.180.33 ± 0.17cP < 0.01.HDL3 cholesterol (mmol/l)0.76 ± 0.140.76 ± 0.13aNot significant.LDL cholesterol (mmol/l)2.76 ± 0.673.15 ± 0.61aNot significant.ApoA-I (g/l)1.29 ± 0.201.19 ± 0.26aNot significant.ApoB (g/l)0.70 ± 0.150.79 ± 0.16aNot significant.Lp(a) (g/l)0.17 ± 0.250.18 ± 0.27aNot significant.Apo E genotype (n)ε2/ε352aNot significant.ε3/ε31910aNot significant.ε2/ε410aNot significant.ε3/ε454aNot significant.ApoA-IV phenotype (n)A-IV 0/101aNot significant.A-IV 1/12712aNot significant.A-IV 1/233aNot significant.Data are means ± SD. Apo, apolipoprotein; Lp(a), lipoprotein (a).a Not significant.b P < 0.05.c P < 0.01. Open table in a new tab Data are means ± SD. Apo, apolipoprotein; Lp(a), lipoprotein (a). The distribution of apoE genotypes and apoA-IV phenotypes were not statistically different between controls and obese subjects (Table 2). The three apoE genotypes had comparable clinical characteristics and lipid values. Furthermore, clinical characteristics and lipid parameters were not different between apoA-IV 1/1 and 1/2 phenotypes. TG responses after the OLFT and plasma apoA-IV levels at different time points (T0, T4, and T8) are shown in Table 3. Plasma levels of apoA-IV levels at T0 (fasting), at T4, and at T8 were significantly higher in obese subjects than in controls. The area under the plasma apoA-IV curve (AUC apoA-IV) was significantly greater in obese subjects. Plasma TG at T8 and nonchylomicron TG at T8 were significantly higher in obese subjects than in controls (P < 0.05). The AUC of plasma TG and the AUC of chylomicron TG were not significantly different between controls and obese subjects. The incremental AUC for plasma TG was not different between controls and obese subjects. The AUC of nonchylomicron TG and the incremental AUC of nonchylomicron TG were significantly greater in obese subjects than in controls (P < 0.05).TABLE 3.Triglyceride and apoA-IV responses after oral fat load test (OFLT) in control and obese subjectsControls (n = 30)Obese Subjects (n = 16)Plasma TG at T0 (mmol/l)0.77 ± 0.320.93 ± 0.23aNot significant.Plasma TG at T2 (mmol/l)1.47 ± 0.661.43 ± 0.43aNot significant.Plasma TG at T3 (mmol/l)1.67 ± 0.801.70 ± 0.55aNot significant.Plasma TG at T4 (mmol/l)1.75 ± 0.791.74 ± 0.48aNot significant.Plasma TG at T5 (mmol/l)1.79 ± 0.771.67 ± 0.60aNot significant.Plasma TG at T6 (mmol/l)1.46 ± 0.581.53 ± 0.51aNot significant.Plasma TG at T8 (mmol/l)0.93 ± 0.441.24 ± 0.46bP < 0.05.CM TG at T0 (mmol/l)00aNot significant.CM TG at T2 (mmol/l)0.52 ± 0.380.35 ± 0.22aNot significant.CM TG at T3 (mmol/l)0.62 ± 0.460.48 ± 0.34aNot significant.CM TG at T4 (mmol/l)0.71 ± 0.420.50 ± 0.22aNot significant.CM TG at T5 (mmol/l)0.74 ± 0.480.50 ± 0.26aNot significant.CM TG at T6 (mmol/l)0.53 ± 0.280.47 ± 0.25aNot significant.CM TG at T8 (mmol/l)0.25 ± 0.210.31 ± 0.18aNot significant.Non-CM TG at T0 (mmol/l)0.77 ± 0.320.93 ± 0.23aNot significant.Non-CM TG at T2 (mmol/l)0.96 ± 0.361.09 ± 0.29aNot significant.Non-CM TG at T3 (mmol/l)1.05 ± 0.391.22 ± 0.31aNot significant.Non-CM TG at T4 (mmol/l)1.04 ± 0.411.24 ± 0.34aNot significant.Non-CM TG at T5 (mmol/l)1.03 ± 0.391.18 ± 0.43aNot significant.Non-CM TG at T6 (mmol/l)0.93 ± 0.361.06 ± 0.35aNot significant.Non-CM TG at T8 (mmol/l)0.68 ± 0.270.93 ± 0.33cP < 0.01.AUC plasma TG (mmol/l · min)659 ± 205705 ± 182aNot significant.AUCi plasma TG (mmol/l · min)321 ± 160259 ± 106aNot significant.AUC CM TG (mmol/l · min)176 ± 70136 ± 57aNot significant.AUC non-CM TG (mmol/l · min)426 ± 119516 ± 138bP < 0.05.AUCi non-CM TG (mmol/l · min)91 ± 58127 ± 57bP < 0.05.Fasting apoA-IV at T0 (mg/l)124.0 ± 22.813

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