Pascal Lebel

Short term response of circulating leptin to feeding and fasting in man: influence of circadian cycle.

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±2.2 ng/ml to a value of 4.5±2.7 ng/ml (P<0.01) 8 h after the fatty meal. Second experiment. During the day, serum leptin levels increased progressively from 2.65±1.7 to 3.34±2.2 ng/ml (P<0.001) 6 h after the test-meal and decreased from 2.68±1.5 to 1.9±1.1 ng/ml (P<0.001) 8 h after the beginning of the fasting experiment. Similar results were obtained at night. No statistically significant differences in leptin levels were observed between day and night sessions in response to feeding (mean area under the curve: 3.0±4.1 vs 4.1±4.1 ng/ml) and fasting (−2.9±2.2 vs −1.5±2.2 ng/ml).CONCLUSION: In two independent experiments, human serum leptin levels increase following food intake. This response is not influenced by nycthemeral cycle.

Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake

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.

Postprandial Leptin Response to Carbohydrate and Fat Meals in Obese Women

Objective: To assess the postprandial leptin responses to a carbohydrate and a fatty meal in obese subjects and its association with postprandial insulin response. Methods: Eight obese and 11 lean women were given, in a random order, an isocaloric carbohydrate meal (3.43 MJ, 166g of carbohydrates, 38g of proteins) or fat meal (3.35 MJ, 70g of fat, 36g of proteins) or remained fasting. Blood samples were collected hourly during the nine hours after the meal for leptin, insulin, C-peptide and glucose determinations. Results: In obese subjects, as in lean subjects, postprandial leptin response, calculated as the increment above fasting values, was higher after the carbohydrate meal than after the fatty meal (p < 0.01). However, after the carbohydrate meal, postprandial leptin increment was lower (p < 0.05) in obese subjects than in lean controls. In contrast, there was no difference in postprandial leptin response between lean and obese subjects after the fatty meal. Correlation analyses showed that the area under the postprandial leptin response curve (leptin AUC) was correlated to insulin AUC in lean (r = 0.70, p < 0.01), but not in obese subjects. Conclusion: 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.

Parental history of early myocardial infarction is associated with decreased levels of lipoparticle AI in adolescents.

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) low-density 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 (P < .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.

Fat ingestion is associated with increased levels of apoC‐III‐ and apoE‐B‐containing lipoprotein particles in humans

Apolipoprotein (apo) C‐III and apoE have a major influence on post‐prandial apoB‐containing lipoprotein metabolism. The goal of the present study was to compare the post‐prandial changes in particles containing apoB and apoC‐III and those containing apoB and apoE. Twenty subjects consumed a fatty meal (1 g of fat kg−1). Human lipoprotein particles were measured by enzyme‐linked immunosorbent assay (ELISA) using combinations of anti‐apoC‐III, ‐apoE and ‐apoB. Post‐prandial lipaemia was associated with an increase in LpC‐III:B (+ 100%) and LpE:B (+ 55%; P < 0.05), which occurred 4.07 ± 1.2 and 4.7 ± 0.8 h after the meal respectively (P < 0.05). Gel filtration chromatography showed that fasting plasma LpC‐III:B and LpE:B eluted in two fractions consisting of large and smaller sized particles; 3 h after the meal, LpC‐III:B and LpE:B increased in the very low‐density lipoprotein (VLDL) + intermediate‐density lipoprotein (IDL) fraction; at 6 h, LpC‐III:B and LpE:B decreased in VLDL and LpE:B increased moderately in the low‐density lipoprotein (LDL) size range; at 10 h, both concentrations of lipoprotein particles returned to fasting levels. In conclusion, apoC‐III‐B‐containing and apoE‐B‐containing lipoproteins have different post‐prandial metabolic fates. These differences may result in different atherogenic potential.

Postprandial lipaemia is associated with increased levels of apolipoprotein A-IV in the triacylglycerol-rich fraction and decreased levels in the denser plasma fractions.

Apolipoprotein (apo) A-IV is primarily associated with HDL or with the lipoprotein-free fraction of plasma, and in small amounts with chylomicrons and VLDL. The aim of the present study was to assess the effect of a fatty meal on the postprandial variation in plasma apo A-IV and on its distribution among lipoprotein fractions following absorption of fat. Twenty healthy male subjects participated in the study. After an overnight fast, subjects were given a fatty breakfast containing 1 g fat/kg body weight (% energy: fat 65, carbohydrate 20; protein 15). Blood samples were taken every hour during the next 10 h. Apo A-IV was measured by ELISA. Postprandial lipaemia was associated with a moderate, although significant, increase in the plasma levels of apo A-IV. Apo A-IV increased from the median baseline value of 0.15 g/l to 0.165 g/l (median +17%; P < 0.01) 5 h after fat ingestion. The postprandial peak of apo A-IV occurred 1 h after the triacylglycerol peak. There were no statistically significant correlations between baseline lipids, baseline apo A-IV and postprandial changes in apo A-IV levels, or between postprandial changes in lipids and apo A-IV at any time. To assess apo A-IV distribution among lipoproteins, plasma was fractionated by fast performance liquid chromatography at baseline and 3, 6 and 10 h postprandially. There was a substantial heterogeneity in the apo A-IV distribution among lipoproteins following the fatty meal. At 3 h after fat ingestion, apo A-IV levels increased in the triacyglycerol-rich lipoprotein (TRL) fraction and decreased in the denser plasma fraction. At 6 h after the fatty meal, apo A-IV was still present in the TRL but was decreased in the HDL fractions. The findings of the present study support the concept that apo A-IV particles transfer from the denser plasma fraction to TRL during postprandial lipaemia.