Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor implicated in adipocyte differentiation, lipid and glucose metabolism. A polymorphism corresponding to a silent C-->T substitution was detected in exon 6 of the PPAR gamma gene. We analysed the relationships between this genetic polymorphism and various markers of the obesity phenotype (body weight, body mass index, waist:hip ratio and plasma leptin levels) in a representative sample of 820 men and women living in northern France. The frequencies of the C and T alleles were 0.860 and 0.140 respectively. In the whole sample no association of the polymorphism with the markers tested was observed but a statistically significant interaction ( P < 0.03) existed between this polymorphism and body mass index for plasma leptin levels. This result suggested that the impact of the PPAR gamma gene polymorphism on plasma leptin levels differed according to the BMI of the subjects. Indeed, obese subjects (BMI >30 kg/m2) bearing at least one T allele ( CT + TT ) had higher plasma leptin levels than subjects who did not (35.0 +/- 17.4 ng/ml versus 28.3 +/- 14.8 ng/ml respectively; P < 0.001). This effect existed in both genders, despite the higher plasma leptin levels observed in women. The plasma leptin level increase was not associated with elevation of body mass index, even though these two variables were highly correlated. Thus for a given leptin level the BMI was relatively lower in obese subjects carrying at least one T allele than in obese CC homozygotes. Our results show that in obese subjects variability within the PPAR gamma gene locus is associated with circulating leptin levels and may modify the relationship between leptin levels and adipose tissue mass.

To assess the impact of the macronutrient content of a meal on the postprandial leptin response and its relationship with postprandial satiety, 22 young healthy subjects (11 men and 11 women) were given, in a randomized order, an isoenergetic meal [carbohydrate (81%) or fat (79%)] or remained fasting. Blood sampling and hunger and satiety scores were collected hourly during 9 h after the meal. Spontaneous intake was measured at a buffet meal at 9 h postprandially. In both genders, leptin response was higher after the carbohydrate meal than after the fat meal and while fasting. In women, leptin levels were higher after the fat meal than while fasting. Leptin response was significantly correlated to insulin response (r = 0.51, P < 0.0001). Hunger and satiety ratings and subsequent energy intake were not different after carbohydrate or fat intake. In conclusion, a carbohydrate meal induces higher postprandial leptin levels than an isoenergetic fat meal. Short-term regulation of postprandial satiety and food intake is not influenced by circulating leptin.

OBJECTIVE: To investigate whether acute feeding induces changes in circulating leptin levels in humans and whether these changes vary according to nycthemeral cycle. METHODS: First experiment. Eighteen male subjects were given a fatty meal at 08.00 h. Blood sampling was performed for 10 h following this meal. Second experiment. Thirteen male subjects were given either a mixed meal or remained fasting either at night (starting at 01.00 h) or during the day (starting at 13.00 h). Blood samples were drawn every hour for a period of 8 h. RESULTS: First experiment. Serum leptin levels increased progressively from a mean (s.d.) baseline of 3.8 AE 2.2 ngaml to a value of 4.5 AE 2.7 ngaml (P`0.01) 8 h after the fatty meal. Second experiment. During the day, serum leptin levels increased progressively from 2.65 AE 1.7 to 3.34 AE 2.2 ngaml (P`0.001) 6 h after the test-meal and decreased from 2.68 AE 1.5 to 1.9 AE 1.1 ngaml (P`0.001) 8 h after the beginning of the fasting experiment. Similar results were obtained at night. No statistically signi®cant differences in leptin levels were observed between day and night sessions in response to feeding (mean area under the curve: 3.0 AE 4.1 vs 4.1 AE 4.1 ngaml) and fasting (72.9 AE 2.2 vs 71.5 AE 2.2 ngaml). CONCLUSION: In two independent experiments, human serum leptin levels increase following food intake. This response is not in¯uenced by nycthemeral cycle.

The goal of the present study was to assess the influence of mealtime on postprandial lipemia. Thirteen healthy subject aged 19-32 y were given the same meal at night (0100) or during the day (1300) in random order: the meal contained 40% of estimated daily energy expenditure. Blood samples were drawn at baseline and hourly for 8 h after the meal. Serum total cholesterol, very-low-density-lipoprotein cholesterol (VLDL-C), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), triacylglycerols, VLDL-triacylglycerols, apolipoprotein (apo) A-I, and apo B were measured at each time point. In a subgroup of seven subjects a control fasting reference line was measured according to the same nocturnal and diurnal time schedule. The mean postprandial concentrations of triacylglycerol (P < 0.001), VLDL-triacylglycerol (P < 0.001), and VLDL-C (P < 0.001) were higher at night than during the day. In contrast, mean cholesterol (P < 0.01), LDL-C (P < 0.01), HDL-C (P < 0.001), apo A-I (P < 0.001), and apo B (P < 0.001) concentrations were lower after the night meal than after the day meal. The magnitude of the postprandial response was estimated by the area between the fasting and postprandial curves. The triacylglycerol and VLDL-triacylglycerol responses were not significantly different between night and day. The VLDL-C (P < 0.01) response was greater and LDL-C (P < 0.0001) and HDL-C (P < 0.01) responses were lower at night than during the day. These results indicate that circadian factors specifically affect serum cholesterol transport. Apo B (P < 0.01) and apo A-I (P < 0.01) responses followed LDL-C and HDL-C changes during the day but were dissociated from lipoprotein responses at night, suggesting that circadian apolipoprotein regulation is dissociated from that of serum lipids. The results of the present study indicate that postprandial lipid, lipoprotein, and apolipoprotein concentrations are affected by circadian factors.

These results indicate that postprandial leptin response is lower after a carbohydrate meal in obese women than in lean controls, suggesting an impairment of postprandial leptin regulation in obese women.

The goal of the present study was to compare the plasma lipid responses of massively obese and lean women to a fat load and a carbohydrate load. For this purpose, 11 lean [body mass index (BMI), 21.6 +/- 2 kg/m(2)] and 8 obese (BMI, 50.8 +/- 7 kg/m(2)) normolipidemic women were given, in random order, either a dietary carbohydrate load (3.43 MJ, 166 g carbohydrates, 38 g proteins) or a dietary fat load (3.35 MJ, 70 g fat, 36 g proteins). Blood samples were collected hourly for 9 h after the test meal for measurements of triglyceride-rich lipoprotein (TRL)-lipid, apolipoprotein (apo)B-48 and apoB-100. Triglycerides (P < 0.0001), TRL triglycerides (P < 0.0001), TRL cholesterol (P < 0.04) and apoB-48 (P < 0.0001) peaked 3 h after the fat meal and returned progressively to baseline values in both obese women and lean controls. These lipid and apolipoprotein changes did not differ between the two groups. In contrast, after the carbohydrate load, the plasma triglyceride (P < 0.0001) and TRL triglyceride (P < 0.0001) increments were significantly greater in obese women than in lean controls. This carbohydrate-induced TRL triglyceride increment was half of that following the isocaloric fat load. The carbohydrate load did not affect apoB-100 and apoB-48 levels. These findings suggest that postprandial triglyceride metabolism is impaired after a carbohydrate load in normolipidemic massively obese women.

A family history of coronary heart disease (CHD) is a known risk factor for CHD. To investigate the possible role of lipoprotein particles in the relationship between family history of CHD and risk of CHD, we performed a case-control study in a sample of adolescents. The case group consisted of 97 adolescents whose parents had suffered a verified myocardial infarction before the age of 55 years. The control group was composed of 194 subjects without any family history of CHD. One case patient was matched to two control subjects for gender, age, and body mass index. In both groups, plasma lipid variables were measured, including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), lowdensity lipoprotein cholesterol, apolipoprotein (apo)AI, apoB, apoAI-containing lipoprotein particles without apoAII (LpAI) and with apoAII, and apoB-containing lipoprotein particles with apoE and with apoCIII. Adolescents with a family history of early myocardial infarction had lower plasma levels of HDL-C (/ » <.0001), apoAI (P<.01), and LpAI (P<.0001) than control subjects (adjusted for gender, age, body mass index, smoking habits, and oral contraceptive use). No other differences were statistically significant between case and control subjects. The analysis was repeated separately for male and female subjects. In young men, the best predictor of family history of early myocardial infarction was the LpAI plasma level, whereas in young women it was the HDL-C plasma level. Decreased levels of HDL-C and LpAI lipoprotein particles explain part of the relationship between parental history of early myocardial infarction and CHD risk. (Arterioscler Thromb. 1993;13:1640-1644 KEY WORDS • lipoproteins • LpAI • family history • coronary heart disease • adolescents • risk factors A family history of coronary heart disease (CHD) predicts CHD in adults, 1 which suggests that k. family history may be a useful tool for identifying high-risk subjects at a young age. This increased CHD risk in those with a positive family history is partly related to the familial clustering of known risk factors such as cigarette smoking, obesity, and plasma lipid levels.2 Among these risk factors, abnormalities in lipid metabolism have been extensively studied. Alterations in plasma lipoprotein and apolipoprotein (apo) levels are variously associated with parental history of CHD in children, adolescents, young adults, and adults: plasma low-density lipoprotein cholesterol (LDL-C) and apoB levels are higher 3 ' 4 and high-density lipoprotein cholesterol (HDL-C) and apoAI levels 5 7 are lower in subjects with a family history of CHD.Biochemical and immunological analyses show that these lipoprotein subfractions are heterogeneous and include subpopulations with different lipid and apolipoprotein compositions.8 By using combinations of mono- clonal and polyclonal antibodies directed against apolipoproteins, it is possible to identify HDL subpopulations of apoAI-containing lipoparticles without apoAII (LpAI) or with apoAII (LpAILAI); LDL subp...

Mental stress is associated with increased concentrations of postprandial triacylglycerol-rich lipoprotein fractions. Therefore, postprandial hyperlipidemia is one possible mechanism contributing to the higher risk of ischemic heart disease in stressed people.