Postprandial changes in the distribution of apolipoprotein AIV between apolipoprotein B- and non apolipoprotein B-containing lipoproteins in obese women

Plasma apolipoprotein AIV (apo AIV) level has been shown to be a good marker of triglyceride changes after a high-fat diet. However, the distribution of apo AIV between apo B- and non-apo B-containing lipoproteins (Lp) during the postprandial state has not been described as well as the influence of obesity on this distribution. Our aim was to study the influence of parameters related to obesity and insulin resistance on the postprandial changes in apo AIV-containing Lp after a high-fat meal in obese women. Twenty-three overweight or obese women (body mass index [BMI] ranging from 29.1 and 64.0 kg.1 m(-2)), for whom blood samples were taken after fasting overnight, participated in the study. Thirteen of these obese women were given a fatty meal and, in this case, blood samples were taken at fast and 30 minutes, 1, 2, 4, and 6 hours after ingestion of the fat meal. Apo AIV-containing particle families, Lp B:AIVf (family [f] of particles containing at least apo B and apo AIV) and Lp AIV non-Bf (family [f] of particles containing apo AIV, but free of apo B) were quantified by sandwich enzyme-linked immunosorbent assay (ELISA). When fasting, Lp B:AIVf and Lp AIV non-Bf did not correlate with any of the parameters related to obesity and insulin resistance, if one excepts a positive correlation between HDL-cholesterol (HDL-C) and Lp AIV non-Bf. Postprandial lipemia was associated with a trend towards an increase in the plasma levels of apo AIV-containing Lp 6 hours after fat ingestion. The postprandial peak of Lp B:AIVf and Lp AIV non-Bf occurred 2 hours after the triglyceride peak. The distribution between apo B- and non-apo B-containing Lp did not change after ingestion of the fat meal, if one excepts a tendancy towards a lower ratio of bound and nonbound forms at 8 hours. Fasting plasma Lp B:AIVf concentration correlated with the area under the curve (AUC) of plasma triglycerides (beta = 0.11, P <.02). In a multivariate analysis, BMI (beta = 51.85, P <.001), fasting triglycerides (beta = 431.08, P <.01), and low-density lipoprotein-cholesterol (LDL-C) (beta = 2638.57, P <.005) were independent and positive determinants of the AUC of Lp AIV non-Bf, while waist circumference (beta = -23.94, P <.001), cholesterol (beta = -1655.02, P <.01), and systolic blood pressure (beta = -6.34, P <.05) were negative and independent determinants of this AUC. Fasting Lp B:AIVf may represent a good marker of the postprandial triglyceride increase in obese women. Changes in apo AIV concentrations in apo B- and non-apo B-containing Lp after a fat meal depend mainly on the degree of obesity rather than on insulin resistance. This effect is more obvious for Lp AIV non-Bf than for Lp B:AIVf.     

Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight

OBJECTIVE: To evaluate whether postprandial abnormalities of energy expenditure and/or lipid oxidation are present in healthy, normal-weight subjects with a strong family history of obesity and thus at high risk to become obese. DESIGN: Case-control study. SUBJECTS: A total of 16 young healthy men participated in the study. Eight subjects had both parents overweight (father's and mother's body mass index (BMI) >25 kg/m(2)) and eight had both parents with normal body weight (father's and mother's BMI<25 kg/m(2), respectively). The group of subjects with overweight parents was similar to that with normal-weight parents (control group) in terms of BMI (23.7+/-1.7 vs 22.7+/-1.1 kg/m(2)) (M+/-s.d.) and fat-free body mass (FFM) (60.5+/-4.9 vs 58.4+/-2.0 kg), but was slightly older than the control group (25.4+/-3.3 vs 22.7+/-2.4 y; P<0.05). MEASUREMENTS: Energy expenditure (EE) was measured by indirect calorimetry, and blood samples were taken for the evaluation of metabolic variables in the fasting state and every hour for 8 h after a standard fat-rich meal (protein 15%, carbohydrate 34%, fat 51%, 4090 kJ). RESULTS:: Fasting plasma glucose, cholesterol, HDL-cholesterol, triglyceride, free fatty acid (FFA) and leptin concentrations were similar in both groups of participants, but subjects with overweight parents has significantly lower plasma insulin concentrations (5.11+/-0.51 vs 7.07+/-1.56 microU/ml; P<0.007) and HOMA index of insulin resistance (1.1+/-0.1 vs 1.6+/-0.4; P<0.01). Postprandial plasma glucose, triglyceride, FFA and leptin concentrations were similar in the two groups, whereas insulin levels were significantly lower in the group with both parents overweight at 3, 5, 6, 7 and 8 h. Fasting and postprandial EE, and fasting lipid and carbohydrate oxidation were similar in both groups. On the contrary, postprandial carbohydrate oxidation (incremental area under curve) was significantly higher (196.25+/-94.75 vs 75.88+/-74.72 mg/kg FFM x 8 h; P<0.007) and that of lipid oxidation lower (90.93+/-80.32 vs 163.68+/-108.22 mg/kg FFM x 8 h; P<0.05) in the group of subjects with overweight parents. CONCLUSION: Normal-weight subjects with a strong family history of obesity present a reduced lipid oxidation in the postprandial period and a metabolic profile characterized by low plasma insulin levels and the HOMA index, which is compatible with increased insulin sensitivity. These metabolic characteristics may be considered as early predictors of weight gain and are probably genetically determined.     

Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight

OBJECTIVE: To evaluate whether postprandial abnormalities of energy expenditure and/or lipid oxidation are present in healthy, normal-weight subjects with a strong family history of obesity and thus at high risk to become obese. DESIGN: Case-control study. SUBJECTS: A total of 16 young healthy men participated in the study. Eight subjects had both parents overweight (father's and mother's body mass index (BMI) >25 kg/m(2)) and eight had both parents with normal body weight (father's and mother's BMI<25 kg/m(2), respectively). The group of subjects with overweight parents was similar to that with normal-weight parents (control group) in terms of BMI (23.7+/-1.7 vs 22.7+/-1.1 kg/m(2)) (M+/-s.d.) and fat-free body mass (FFM) (60.5+/-4.9 vs 58.4+/-2.0 kg), but was slightly older than the control group (25.4+/-3.3 vs 22.7+/-2.4 y; P<0.05). MEASUREMENTS: Energy expenditure (EE) was measured by indirect calorimetry, and blood samples were taken for the evaluation of metabolic variables in the fasting state and every hour for 8 h after a standard fat-rich meal (protein 15%, carbohydrate 34%, fat 51%, 4090 kJ). RESULTS: Fasting plasma glucose, cholesterol, HDL-cholesterol, triglyceride, free fatty acid (FFA) and leptin concentrations were similar in both groups of participants, but subjects with overweight parents has significantly lower plasma insulin concentrations (5.11+/-0.51 vs 7.07+/-1.56 microU/ml; P<0.007) and HOMA index of insulin resistance (1.1+/-0.1 vs 1.6+/-0.4; P<0.01). Postprandial plasma glucose, triglyceride, FFA and leptin concentrations were similar in the two groups, whereas insulin levels were significantly lower in the group with both parents overweight at 3, 5, 6, 7 and 8 h. Fasting and postprandial EE, and fasting lipid and carbohydrate oxidation were similar in both groups. On the contrary, postprandial carbohydrate oxidation (incremental area under curve) was significantly higher (196.25+/-94.75 vs 75.88+/-74.72 mg/kg FFM x 8 h; P<0.007) and that of lipid oxidation lower (90.93+/-80.32 vs 163.68+/-108.22 mg/kg FFM x 8 h; P<0.05) in the group of subjects with overweight parents. CONCLUSION: Normal-weight subjects with a strong family history of obesity present a reduced lipid oxidation in the postprandial period and a metabolic profile characterized by low plasma insulin levels and the HOMA index, which is compatible with increased insulin sensitivity. These metabolic characteristics may be considered as early predictors of weight gain and are probably genetically determined.     

Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity

This study determined whether reductions in postprandial plasma nonesterified fatty acid (FFA) flux would lead to reductions in plasma acylcarnitine (AC) concentrations. Plasma AC was measured by liquid chromatography with tandem mass spectrometry in the fasting state and over 6 hours after a high-fat (50% energy) meal was fed to 16 overweight and obese subjects with a wide range of insulin sensitivities. Body composition was measured by dual-energy x-ray absorptiometry; insulin sensitivity by insulin-modified, frequently sampled intravenous glucose tolerance test; substrate oxidation by indirect calorimetry; blood metabolite and hormone concentrations biochemically; and fatty acid flux by using stable isotope tracers. Lean body mass and fasting fat oxidation correlated positively (r > 0.522, P < .05), whereas glucose oxidation correlated negatively (r < -0.551, P < .04), with fasting AC. Postprandially, plasma glucose, insulin, and triglyceride concentrations increased; and FFA concentrations decreased significantly. The responses of plasma AC species depended on chain length and saturation, with C14:0, C16:0, and C18:0 remaining unchanged, and unsaturated species (eg, C14:1, C14:2) falling significantly (21%-46%, P < .03). Postmeal nadir AC concentrations were positively associated with lean body mass, postprandial fatty acid flux, and FFA concentrations (r > 0.515, P < .05). By contrast, nadir AC correlated negatively with insulin sensitivity and spillover of meal-derived fatty acids (r < -0.528, P < .04). Conditions that impact fatty acid flux contribute to the control of postprandial plasma AC concentrations. These data underscore the need for a better understanding of postprandial fatty acid oxidation and dietary fat delivery in the setting of adipose insulin resistance to determine how postprandial lipemia contributes to chronic disease risk.     

The influence of the type of dietary fat on postprandial fat oxidation rates: monounsaturated (olive oil) vs saturated fat (cream)

OBJECTIVE: To compare postprandial whole-body fat oxidation rates in humans, following high-fat (43% of total energy) mixed breakfast meals, of fixed energy and macronutrient composition, rich in either monounsaturated fat (MUFA) from extra virgin olive oil or saturated fat (SFA) from cream. DESIGN: Paired comparison of resting metabolic rate (RMR), thermic effect of a meal and substrate oxidation rates following consumption of isocaloric breakfast meals, differing only in the type of fat, administered in random order 1-2 weeks apart. SUBJECTS: Fourteen male volunteers, body mass index (BMI) in the range 20-32 kg/m(2), aged 24-49 y and resident in Melbourne, Australia, were recruited by advertisement in the local media or by personal contact. MEASUREMENTS: Body size and composition was determined by anthropometry and dual energy X-ray absorptiometry (DEXA). Indirect calorimetry was used to measure RMR, thermic effect of a meal, post-meal total energy expenditure and substrate oxidation rate. Blood pressure and pulse rates were measured with an automated oscillometric system. Fasting and 2 h postprandial glucose and insulin concentrations and the fasting lipid profile were also determined. RESULTS: In the 5 h following the MUFA breakfast, there was a significantly greater postprandial fat oxidation rate (3.08+/-4.58 g/5 h, P=0.017), and lower postprandial carbohydrate oxidation rate (P=0.025), than after the SFA breakfast. Thermic effect of a meal was significantly higher (55 kJ/5 h, P=0.034) after the MUFA breakfast, in subjects with a high waist circumference (HWC > or = 99 cm) than those with a low waist circumference (LWC<99 cm). This difference was not detected following the SFA breakfast (P=0.910). CONCLUSION: If postprandial fat oxidation rates are higher after high MUFA, rather than SFA meals, then a simple change to the type of dietary fat consumed might have beneficial effects in curbing weight gain in men consuming a relatively high-fat diet. This may be particularly evident in men with a large waist circumference.     

Ghrelin secretion in severely obese subjects before and after a 3-week integrated body mass reduction program

Ghrelin, the endogenous ligand of GH-secretagogue receptors, has been implicated in the regulation of feeding behavior and energy balance. Aim of the study was to investigate ghrelin levels in fasting conditions and after a standard meal test in obese subjects before and after a 3-week integrated body weight reduction (BWR) program (consisting of energy-restricted diet, exercise training, psychological counselling and nutritional education). Weight, height, fat mass, fat free mass (by impedentiometry), circulating ghrelin, insulin and leptin levels were evaluated in 10 obese subjects (3 male, 7 female; mean age: 35 +/- 9.3 yr; body mass index BMI: 45.2 +/- 10.6 kg/m2) before and after weight reduction. At baseline, obese subjects showed significantly lower ghrelin levels than controls, which were negatively correlated with BMI, weight, insulin and leptin levels. Fasting ghrelin levels were not modified by standard meal test in obese subjects (from 110.8 +/- 69.7 to 91.8 +/- 70.2 pmol/l p=ns), while a significant reduction was observed in controls (from 352.4 +/- 176.7 to 199.0 +/- 105.2 pmol/l; p<0.01). After a 3-week integrated BWR program obese subjects significantly reduced weight, BMI and leptin levels, while no significant changes were found both in fasting ghrelin and in ghrelin response after the meal. In conclusion, 5% weight loss obtained after a short-term period of integrated BWR program is not sufficient to normalize fasting ghrelin levels nor to restore the normal ghrelin suppression after a meal in severely obese subjects.     

Unchanged fasting and postprandial adiponectin levels following a 4-day caloric restriction in young healthy men

OBJECTIVE: Adiponectin is an adipocyte-secreted protein that has been shown to promote fat oxidation and insulin sensitivity in animals. Whether acute energy restriction is associated with modulation of adiponectin in humans remains largely unknown. The purpose of this study was to examine the effects of a short-term caloric restriction on fasting and postprandial adiponectin levels in young healthy men. RESEARCH DESIGN AND METHODS: Fifteen young healthy men were subjected to a 4-day energy restricted diet (-800 kcal/day). Before and after the intervention, anthropometric measurements, fasting and postprandial glucose, insulin and adiponectin were measured at 0, 30 and 60 min after a fixed breakfast. RESULTS: While fat mass remained stable, minor but significant changes in weight were observed after the 4-day energy-restricted diet. Glucose and insulin levels increased postprandially, and patterns did not differ before and after the intervention. Fasting levels of adiponectin remained unchanged after the energy restriction, and postprandial levels were not significantly different from fasting levels either before, or after, the intervention. CONCLUSIONS: Fasting and postprandial adiponectin levels are not acutely modulated by a short-term energy restriction in young healthy men.     

Fasting and daylong triglycerides in obesity with and without type 2 diabetes

Postprandial hypertriglyceridemia associated with insulin resistance is one of the cardiovascular risk factors in obesity and type 2 diabetes. It is not known whether diabetics have a more pronounced postprandial hypertriglyceridemia than obese subjects. Daylong triglyceridemia, representing postprandial lipemia, was determined in obese subjects with and without type 2 diabetes and in lean subjects. Nineteen type 2 diabetics (F/M: 7/12, body mass index [BMI]: 30.6 +/- 5.4 kg/m(2)), 45 obese nondiabetics (F/M: 16/29, BMI: 29.5 +/- 2.6 kg/m(2)) and 78 lean subjects (F/M: 28/50, BMI: 23.7 +/- 2.2 kg/m(2)) measured capillary triglycerides (TGc) during 3 days on 6 fixed time-points each day in an out-of-hospital situation. Daylong TGc profiles were calculated as mean integrated area under the TGc-curve (TGc-AUC). Fasting plasma TG were higher in diabetics and obese nondiabetics (1.81 +/- 0.79 and 1.77 +/- 0.80 mmol/L) compared with lean subjects (1.23 +/- 0.67 mmol/L, P <.001). TGc-AUC was similarly increased in both diabetics and obese nondiabetics (35.0 +/- 12.1 and 35.2 +/- 10.6 mmol.1 h/L) compared with lean controls (25.5 +/- 12.0 mmol.1 h/L, P <.001). Self-reported energy intake was not significantly different between the groups. Fasting TGc (r =.87, P <.001) and waist circumference (r =.51, P <.001) were the parameters best associated with TGc-AUC. Using stepwise multiple regression analysis, fasting TGc, BMI, total cholesterol, and high-density lipoprotein (HDL) cholesterol were the best predictors of TGc-AUC, explaining 77% of the variation. The cut-off level for "normal" TGc-AUC, calculated as the 75th percentile of TGc-AUC in lean subjects, was 30.7 mmol.1 h/L and corresponded with a fasting TGc of 1.8 mmol/L (eg, 1.6 mmol/L in plasma), calculated using univariate regression analysis. In conclusion, daylong triglyceridemia is similarly increased in diabetics and obese nondiabetics compared with lean subjects. Fasting TG and central obesity largely determine daylong triglyceridemia, independent of the presence of type 2 diabetes. Decreasing fasting plasma TG below 1.6 mmol/L could lead to a normalization of postprandial lipemia in obese subjects with and without diabetes.     

Plasma leptin is influenced by diet composition and exercise

OBJECTIVE: A low-fat, high-carbohydrate diet (相似文献   

Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women

OBJECTIVE: The purpose of this study was to determine changes in adiponectin levels with moderate weight loss, weight loss plus aerobic exercise, or weight loss plus resistive exercise in overweight and obese, sedentary postmenopausal women. DESIGN: Longitudinal, clinical intervention study of 6-month (3 x /week) program of either weight loss (WL, n=15), weight loss + aerobic exercise (WL+AEX, n=16), or weight loss + resistive exercise (WL+RT, n=9) SUBJECTS: We studied 40 sedentary, overweight and obese (body mass index, BMI=32+/-1 kg/m(2), X+/-s.e.m.) postmenopausal (57+/-1y) women. MEASUREMENTS: Fat mass and fat-free mass (FFM) by dual-energy X-ray absorptiometry, plasma insulin, leptin, and adiponectin by radioimmunoassay. RESULTS: Age, body weight, BMI, waist and hip circumferences, waist-to-hip ratio, VO(2)max, percent fat, total body fat mass, FFM, and fasting plasma glucose, insulin, leptin, and adiponectin concentrations were similar among WL, WL+AEX, and WL+RT groups before the interventions. In all women combined, body weight, BMI, and waist and hip circumferences decreased (P < 0.001). There was a significant absolute decrease in percent body fat from 47 to 44%, representing a 13% decrease in total fat mass and a -1.6% change in FFM. Fasting concentrations of plasma adiponectin did not change (40+/-16%, P=NS), whereas fasting plasma glucose, insulin, and leptin all decreased (P<0.001). CONCLUSIONS: Plasma adiponectin levels do not change with a 6-month moderate weight reduction program even when accompanied by aerobic or resistive exercise training in overweight and obese postmenopausal women.     

Relationship between altered postprandial lipemia and insulin resistance in normolipidemic and normoglucose tolerant obese patients

OBJECTIVE: Although there are changes in the postprandial lipid responses of obese patients, these are closely associated with high fasting triglycerides (TG). This study of 17 normotriglyceridemic, normoglucose-tolerant android obese subjects (body mass index, BMI = 34.3 +/- 3.1 kg/m2) and 33 normal-weight controls (BMI = 21.8 +/- 1.6 kg/m2) was done to examine their postprandial responses to an oral fat loading test containing retinol (890 calories, 85% fat) and to evaluate the possible association between clinical and biological features of obesity and/or insulin resistance and postprandial lipemia. SUBJECTS AND MEASUREMENTS: Blood samples were taken before giving the fat load and at 2,3,4,5,6 and 8 h after it. Insulin sensitivity was assessed using HOMA, and TG and retinyl palmitate (RP) in the plasma, chylomicrons and non-chylomicron fractions were measured each time. RESULTS: The areas under the curves (AUC) of chylomicron TG for the obese and controls were not different, indicating adequate lipolytic activity. By contrast, the AUC for non-chylomicron TG was significantly greater in the obese than in the controls (512 +/- 135 vs 429 +/- 141 mmol/lmin, P < 0.01). In addition, the AUC for RP in this same fraction was significantly lower in the obese than in the controls (103 +/- 55 vs 157 +/- 88 mg/l min, P < 0.05), suggesting that the TG from endogenous lipoproteins accounted for most of the increase in TG in the non chylomicron fraction. Parameters related to obesity showed no relationship with these postprandial abnormalities, whereas HOMA, which discriminated between the groups, partly explained (r2= 23%, P < 0.01) the significant increase in non-chylomicron TG. CONCLUSIONS: Android obese patients with a fasting TG in the normal range and not different from the fasting TG of lean controls had an abnormal postprandial lipemia response, indicated by a significantly greater TG in the non-chylomicron subfraction than in controls. These alterations may be partly due to postprandial changes in endogenous lipoproteins as a consequence of insulin resistance.     

Influence of weight loss on plasma ghrelin responses to high-fat and high-carbohydrate test meals in obese women

BACKGROUND: Diet-induced weight loss is associated with an increase in fasting ghrelin. The influence of weight loss on postprandial ghrelin response remains discussed, but the specific response to macronutrients is not known. OBJECTIVE: The objective of the study was to assess the influence of weight loss in obese women on the plasma ghrelin response to a fat- or carbohydrate-rich meal. DESIGN: Seventeen obese women (mean body mass index 37.6 +/- 5 kg/m2) were given an energy-restricted diet (800 kcal/d) for 7 wk, followed by a maintenance diet for 1 wk. Before and after the weight reduction diet, each woman was given (in random order) two isoenergetic test meals, corresponding to 40% of daily energy needs. The test meals contained either 80% fat and 20% protein or 80% carbohydrate and 20% protein. Blood samples were collected over a 10-h period. Two-way ANOVA with repeated measures was used to assess the effect of the test meal on variables. RESULTS: Weight loss (-11.2 +/- 1.4 kg) was associated with a significant decrease in baseline plasma insulin (9.7 +/- 4.1 to 7.9 +/- 2.4 mU/ml; P < 0.0001) and leptin (25.9 +/- 8.3 to 17.2 +/- 7.8 ng/ml; P < 0.0001) and an increase in plasma ghrelin (1.86 +/- 1.05 to 2.28 +/- 1.48 ng/ml; P < 0.05). Before weight loss, there was no significant difference in postprandial ghrelin response between the test meals. After weight reduction, the ghrelin response was more pronounced after the carbohydrate test meal than after the fat test meal (P < 0.02). CONCLUSION: Weight loss is associated with an improved postprandial plasma ghrelin response to a carbohydrate meal, whereas the response to a fat meal is not modified.     

Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion.

AIMS: Hyperproinsulinaemia is associated with obesity and is a risk factor for Type 2 diabetes. We explored the dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in subjects who had undergone gastric bypass (GBP) surgery compared with morbidly obese (MO) subjects and normal weight control subjects (NW). METHODS: Subjects free from diabetes were recruited: 10 previously MO subjects [body mass index (BMI) +/- sd, 34.8 +/- 6.2 kg/m2] who had undergone GBP surgery, 10 MO subjects (BMI 44 +/- 3.1 kg/m2) and 12 NW control subjects (BMI 23.2 +/- 2.4 kg/m2). After an overnight fast, a standard meal (2400 kJ) was ingested and glucose, proinsulin, insulin free fatty acids and triglycerides were determined up to 180 min. RESULTS: Fasting proinsulin was similar in the GBP group and NW control subjects, but threefold increased in MO subjects (P < 0.05). Postprandial AUC for glucose was similar in the three groups and AUC for proinsulin was high in MO, intermediate in the GBP group and lowest in NW control subjects (P for trend = 0.020). Postprandial proinsulin at 60 min was similar in the GBP group and MO subjects and twofold higher than in NW control subjects. Postprandial proinsulin at 180 min was normal in the GBP group, but fivefold increased in MO subjects (P = 0.008). Insulin increased rapidly at 30 min in the GBP group and was normal at 90 min, whereas insulin was still increased at 90-180 min in the MO subjects (P < 0.001). CONCLUSIONS: MO subjects, free from diabetes, have elevated proinsulin concentrations in the fasting as well as the postprandial phase. After GBP surgery markedly lower fasting and postprandial proinsulin concentrations were observed, although BMI was higher compared with NW control subjects.     

The satiating effect of dietary protein is unrelated to postprandial ghrelin secretion

CONTEXT: Increasing dietary protein relative to carbohydrate and fat enhances weight loss, at least in part by increasing satiety. The mechanism for this is unclear. OBJECTIVE: The objective of this study was to compare the effects of isocaloric test meals with differing protein to fat ratios on fasting and postprandial ghrelin, insulin, glucose, appetite, and energy expenditure before and after weight loss on the respective dietary patterns. DESIGN: The study design was a randomized parallel design of 12 wk of weight loss (6 MJ/d) and 4 wk of weight maintenance (7.3 MJ/d) with meals administered at wk 0 and 16. SETTING: The study was performed at an out-patient research clinic. PATIENTS AND OTHER PARTICIPANTS: Fifty-seven overweight (body mass index, 33.8 +/- 3.5 kg/m2) hyperinsulinemic men (n = 25) and women (n = 32) were studied. Interventions: High-protein/low-fat (34% protein/29% fat) or standard protein/high-fat (18% protein/45% fat) diets/meals were given. MAIN OUTCOME MEASURES: The main outcome measures were weight loss and fasting and postprandial ghrelin, insulin, glucose, appetite, and energy expenditure before and after weight loss. RESULTS: Weight loss (9.2 +/- 0.7 kg) and improvements in fasting and postprandial insulin and glucose occurred independently of diet composition. At wk 0 and 16, subjects wanted less to eat after the high-protein/low-fat than the standard protein/high-fat meal (P = 0.02). Fasting ghrelin increased (157.5 +/- 3.4 pg/ml or 46.6 +/- 1.0 pmol/liter; P < 0.001), and the postprandial ghrelin response improved with weight loss (P = 0.043) independently of diet composition. Postprandial hunger decreased with weight loss (P = 0.018) and was predicted by changes in fasting and postprandial ghrelin (r2 = 0.246; P = 0.004). Lean mass was the best predictor of fasting (r2 = 0.182; P = 0.003) and postprandial ghrelin (r2 = 0.096; P = 0.039) levels. CONCLUSIONS: Exchanging protein for fat produced similar weight loss and improvements in metabolic parameters and ghrelin homeostasis. The reduced appetite observed with increased dietary protein appears not to be mediated by ghrelin homeostasis.     

Ghrelin, insulin sensitivity and postprandial glucose disposal in overweight and obese children

OBJECTIVE: To explore the changes of ghrelin circulating levels induced by a mixed meal and their relationship with postprandial substrate oxidation rates in overweight and obese children with different levels of insulin sensitivity. METHODS: A group of ten boys (age 9-12 years) with different levels of overweight (standard deviation score of body mass index: 1.6-3.2) was recruited. Body composition was measured by dual-energy X-ray absorptiometry. Insulin sensitivity was assessed by a frequently sampled i.v. glucose tolerance test. Pre-prandial and postprandial (3 h) substrate oxidation was measured by indirect calorimetry. The energy content of the test meal (16% protein, 36% carbohydrate and 48% fat) was 40% of pre-prandial energy expenditure (kJ/day). RESULTS: Pre-prandial serum concentration of total ghrelin was 701.4+/-66.9 pg/ml (S.E.M.). The test meal induced a rapid decrease in ghrelin levels and maximal decrease was 27.3+/-2.7% below baseline. Meal intake induced a progressive increase of the carbohydrate oxidation rate for 45 min after food ingestion, followed by a slow decrease without returning to pre-prandial values. Postprandial cumulative carbohydrate oxidation was 16.9+/-0.8 g/3 h. Insulin sensitivity and postprandial maximal decrease of ghrelin concentration showed a significant correlation (r = 0.803, P < 0.01). Moreover, the postprandial carbohydrate oxidation rate correlated with the area under the curve for both insulin (r = 0.673, P < 0.03) and ghrelin (r = -0.661, P < 0.04). CONCLUSIONS: A relevant association between postprandial insulin-mediated glucose metabolism and ghrelin secretion in children with different levels of overweight was found. It is possible that the maintenance of an adequate level of insulin sensitivity and glucose oxidation may affect appetite regulation by favoring a more efficient postprandial ghrelin reduction.     

Postprandial regulation of blood lipids and adipose tissue lipoprotein lipase in type 2 diabetes patients and healthy control subjects

BACKGROUND/AIM: In type 2 diabetes and other insulin-resistant conditions, postprandial hypertriglyceridaemia is an important metabolic perturbation. To further elucidate alterations in the clearance of triglyceride-rich lipoproteins in type 2 diabetes we focused on the nutritional regulation of adipose tissue lipoprotein lipase (LPL). SUBJECTS AND METHODS: Eight subjects with type 2 diabetes and eight age-, sex- and body mass index (BMI)-matched control subjects underwent subcutaneous abdominal adipose tissue biopsies in the fasting state and 3.5 h following a standardized lipid-enriched meal. LPL activity and mass were measured in adipose tissue and also in plasma after an intravenous injection of heparin. RESULTS: Postprandial, but not fasting, triglycerides were significantly higher in the diabetic subjects than in the control subjects (3.0+/-0.4 vs 2.0+/-0.2 mmol/l, P=0.028). Adipose tissue LPL activity was increased following the meal test by approximately 35-55% (P=0.021 and 0.004, respectively). There was no significant difference between the groups in this respect. The specific enzyme activity of LPL was not altered in the postprandial state. Fasting and postprandial adipose tissue LPL activity as well as post-heparin plasma LPL activity tended to be lower among the diabetes patients (NS). There was a significant and independent inverse association between insulin resistance (homeostasis model assessment insulin resistance (HOMA-IR) index) vs post-heparin plasma LPL activity and postprandial triglyceride levels, respectively. Adipose tissue LPL activity was related to insulin action in vitro on adipocyte glucose transport, but not to HOMA-IR. CONCLUSION: Following food intake adipose tissue LPL activity is enhanced to a similar degree in patients with type 2 diabetes and in healthy control subjects matched for BMI, age and gender. If LPL dysregulation is involved in the postprandial hypertriglyceridaemia found in type 2 diabetes, it should occur in tissues other than subcutaneous fat.     

Reliability of the measurement of postprandial thermogenesis in men of three levels of body fatness.

To determine the reliability of the measurement of postprandial thermogenesis by indirect calorimetry and to clarify further the relationship of obesity to thermogenesis in men, the thermic effect of a 720-kcal, mixed liquid meal was compared in 13 lean men (mean +/- SEM, 11.2% +/- 1.4% body fat), 10 average men (22.4% +/- 1.6% body fat), and 12 obese men (33.4% +/- 1.6% body fat) on two occasions. Resting metabolic rate (RMR) was measured for 3 hours: (1) in the fasted state, and (2) after a 720-kcal mixed liquid meal, on two occasions. The thermic effect of the meal, calculated as the postprandial energy expenditure minus the fasting RMR (kcal/3h), was greater for the lean and average men than for the obese men during both trials (P less than .001), but was only marginally different between the lean and average groups (P = .16). The mean values for the two trials were similar and the measurement of thermogenesis was highly reproducible with a reliability coefficient of r = .932 (P less than .001). Across all groups, thermogenesis correlated strongly with percent body fat (r = -.64, P less than .01), but within the average men, thermogenesis was uncorrelated with percent body fat (r = .09) but highly correlated with the glucose response to the meal (r = -.75, P less than .05). Thus, factors other than body fatness, such as insulin sensitivity, may determine thermogenesis within this heterogeneous middle group.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relation between leptin and insulin remains when insulin secretion is disturbed

BACKGROUND: Serum insulin and leptin levels correlate positively. It is not known whether this relation remains the same in cases of severely disturbed insulin secretion and after rapid weight loss. We therefore studied the relation between insulin and leptin in obese type 2 diabetic patients before and after considerable weight loss. METHODS: In 17 obese type 2 diabetic patients, blood glucose-lowering medication was discontinued (day-1) and a 30-day very low calorie diet (VLCD, 450 kcal/day) was started. On days 0, 2, and 30, body weight, body fat mass [with bioelectrical impedance analysis (BIA)], fasting serum glucose, insulin, and leptin were determined. Homeostatic model assessment was used to estimate insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta). On days 2 and 30, an intravenous glucose tolerance test (IVGTT) was performed. RESULTS: Fasting serum leptin levels correlated positively with fasting serum insulin levels (r=0.72, p=0.001 on day 2; r=0.78, p=0.001 on day 30) and area under the curve (AUC) of insulin (r=0.74, p=0.001 on day 2; r=0.84, p=0.0001 on day 30), as well as HOMA-beta, as a measure of insulin secretion, even after correction for body mass index (BMI) and body fat mass, with which leptin was also positively correlated. CONCLUSION: In a group of obese type 2 diabetic patients with a wide range of residual endogenous insulin secretion, we found a positive relation between fasting serum leptin and insulin levels, even after correction for BMI and body fat mass. This was true both before weight loss and during energy restriction with weight loss.     

Fasting and postprandial total ghrelin remain unchanged after short-term energy restriction

Adaptations that promote positive energy balance appear in response to dietary restriction. The aim of this study was to determine whether fasting and postprandial total ghrelin increase in response to short-term energy restriction. Fifteen adult male subjects were subjected to a 4-d energy restricted diet (-800 kcal/d). Body weight and composition, resting energy expenditure, respiratory quotient, fasting and postprandial appetite scores, and fasting and postprandial serum leptin and total ghrelin were determined before and after dietary intervention. Despite the fact that fat mass remained unchanged after the 4 d, fasting (-36%; P 相似文献   

Postprandial lipidemia is normal in non-obese type 2 diabetic patients with relatively preserved insulin secretion

To assess postprandial lipidemia in normotriglyceridaemic type 2 diabetic patients treated with diet only, 12 non-obese patients (8 males, hemoglobin A(1c) [HbA(1c)] 6.80 +/- 0.67%) and 14 controls of similar age, body mass index (BMI), and fasting triglyceride (Tg) were given a test meal (58 g fat, 100,000 IU vitamin A). Fasting low-density lipoprotein (LDL) cholesterol (LDLc), high-density lipoprotein (HDL) cholesterol (HDLc), free fatty acids, and apolipoprotein B (apoB), and fasting and postprandial Tg, retinylpalmitate (RP), LDL size, glucose, and insulin were measured. The homeostasis assessment model (HOMA) index and lipoprotein (Lpl) and hepatic (HL) lipase activities were estimated. Patients showed lower fasting HDLc (1.12 +/- 0.26 v 1.40 +/- 0.28 mmol/L, P =.02) and a trend towards smaller LDL particles, which was significant 4 hours postprandially (25.86 +/- 0.40 v 26.16 +/- 0.30 nm, P =.04). The area under the curve of Tg (AUC-Tg) and RP, and Lpl were similar, but HL was higher in patients (156.63 +/- 23.89 v 118 +/- 43.27 U/L, P =.011). HL correlated inversely with LDL size and directly with the HOMA index. In conclusion, normotriglyceridemic type 2 diabetic patients with insulin resistance but relatively preserved insulin secretion show low fasting HDLc and increased HL, but normal postprandial lipidemia.