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Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol pathway: cellular cholesterol efflux and plasma cholesterol esterification. Eleven healthy middle-aged men consumed four glasses (40 g of alcohol) of red wine, beer, spirits (Dutch gin), or carbonated mineral water (control) daily with evening dinner, for 3 weeks, according to a 4 x 4 Latin square design. After 3 weeks of alcohol consumption the plasma ex vivo cholesterol efflux capacity, measured with Fu5AH cells, was raised by 6.2% (P < 0.0001) and did not differ between the alcoholic beverages. Plasma cholesterol esterification was increased by 10.8% after alcohol (P = 0.008). Changes were statistically significant after beer and spirits, but not after red wine consumption (P = 0.16). HDL lipids changed after alcohol consumption; HDL total cholesterol, HDL cholesteryl ester, HDL free cholesterol, HDL phospholipids and plasma apolipoprotein A-I all increased (P < 0.01). In conclusion, alcohol consumption stimulates cellular cholesterol efflux and its esterification in plasma. These effects were mostly independent of the kind of alcoholic beverage. Chemicals/CAS: Apolipoprotein A-I; Cholesterol Esters; Cholesterol, 57-88-5; Ethanol, 64-17-5; HDL cholesteryl ester; HDL-triglyceride; Lipoproteins, HDL; Phospholipids; Triglycerides

We measured the effects of consumption of moderate amounts of beer, wine or spirits with evening dinner on plasma LDL and HDL levels as well as composition in 11 healthy middle-aged men. Forty grams of alcohol were consumed daily with dinner for a period of 3 weeks. Mineral water was used as a negative control. Dinner was served at 6 pm and blood samples were obtained at 1 h before and 3, 5, 9, and 13 h after the start of the meal. No differences were detected between the effects of the different alcohol- containing beverages. Plasma levels of triglycerides (TG), measured I h before dinner were very variable and higher than fasting values (means of 2.2 and 1.5 mM, respectively). Daily consumption of 40 g of alcohol with dinner resulted in increased postprandial plasma TG levels and decreased low density lipoprotein (LDL) cholesterol concentrations. These effects were transient and observed at 11 pm (TG) and 9 pm and 11 pm (LDL). In contrast, high density lipoproteins (HDL) were raised by alcohol intake at all time points analysed. HDL composition was changed by alcohol consumption, resulting in a raised HDL-cholesterol/apo A-I ratio at 5 pm and 9 pm. The observed alcohol- dependent effects on plasma HDL and LDL during the postprandial phase are considered anti-atherogenic and may contribute to the observed protection against coronary heart disease by moderate alcohol consumption.

Background: Moderate alcohol consumption is associated with a reduced coronary heart disease (CHD) risk. Epidemiologic studies have provided conflicting data which suggests that CHD protection may be modulated or may not be modulated by a person's CHD risk profile. Methods: We examined the effects of moderate alcohol consumption (35 g/day) on postprandial lipoprotein metabolism in two groups of healthy middle-aged men who had different plasma total cholesterol, triglyceride concentrations, and body mass index (BMI), which are three major risk factors for CHD; 11 men had lower plasma lipids and BMI (L-men) and 11 men had higher plasma lipids and BMI (H-men). The effects of alcohol on postprandial lipoprotein metabolism were studied in a crossover design after an acute moderate alcohol intake both after a period of abstinence (alcohol-free beer) and after a period of moderate alcohol consumption (alcohol containing beer). Results: Moderate alcohol consumption changed plasma total cholesterol, total triglycerides, and HDL composition in the postprandial period. Alcohol-induced changes were essentially the same over time in both L-men and H-men. However, changes occurred at a different overall plasma concentration for total cholesterol and total triglycerides. Also, the postprandial response to an acute moderate alcohol dose after a period of abstinence seemed not to essentially differ from the response to an acute moderate alcohol dose after a 4-week period of moderate alcohol consumption. Conclusions: These results suggest that men who differ in risk for CHD, based on plasma lipids and BMI, but without previous or underlying disease, have a similar postprandial lipid response to a moderate dose of alcohol. Chemicals/CAS: Central Nervous System Depressants; Cholesterol, 57-88-5; Cholesterol, HDL; Ethanol, 64-17-5; Triglycerides

The Hyplip2 congenic mouse strain contains part of chromosome 15 from MRL/MpJ on the BALB/cJ background. Hyplip2 mice show increased plasma levels of cholesterol and predominantly triglycerides (TGs) and are susceptible to diet-induced atherosclerosis. This study aimed at elucidation of the mechanism(s) explaining the hypertriglyceridemia. Hypertriglyceridemia can result from increased intestinal or hepatic TG production and/or by decreased LPL-mediated TG clearance. The intestinal TG absorption and chylomicron formation were studied after intravenous injection of Triton WR1339 and an intragastric load of olive oil containing glycerol tri[3H]oleate. No difference was found in intestinal TG absorption. Moreover, the hepatic VLDL-TG production rate and VLDL particle production, after injection of Triton WR1339, were also not affected. To investigate the LPL-mediated TG clearance, mice were injected intravenously with glycerol tri[3H]oleate-labeled VLDL-like emulsion particles. In Hyplip2 mice, the particles were cleared at a decreased rate (half-life of 25 ± 6 vs. 11 ± 2 min; P < 0.05) concomitant with a decreased uptake of emulsion TG-derived 3H-labeled fatty acids by the liver and white adipose tissue. The increased plasma TG levels in Hyplip2 mice do not result from an enhanced intestinal absorption or increased hepatic VLDL production but are caused by decreased LPL-mediated TG clearance. Copyright © 2007 by the American Society for Biochemistry and Molecular Biology, Inc.

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. In this study, postprandial changes in plasma lipids, high-density lipoprotein (HDL) composition and cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activity levels were investigated in response to moderate alcohol consumption. A dose of 40 g of alcohol was consumed as beer, wine or spirits by eight healthy middle-aged men before and during dinner thus simulating social drinking. Lipid parameters were studied before, and at 1, 3, 5, 9, and 13 h after dinner. An alcohol-induced elevation of plasma triglycerides was observed at 3 and 5 h after dinner, but total plasma cholesterol and apolipoprotein B were hardly affected. HDL lipids changed during the postprandial phase after alcohol consumption, HDL triglycerides were elevated at 5 and 9 h, HDL phospholipids were elevated at 9 and 13 h, and HDL cholesterol was elevated at 13 h. A 6% increase in the concentration of apolipoprotein A-II was observed at 13 h. Plasma LCAT activity was slightly increased 9 h after dinner, but CETP activity levels were not affected. The LCAT changes appeared similar for all three alcoholic beverages. It is concluded that moderate alcohol consumption with dinner affects plasma triglyceride concentration as well as HDL composition.Chemicals/CAS: Apolipoproteins; Carrier Proteins; CETP protein, human; Cholesterol Ester Transfer Proteins; Cholesterol, 57-88-5; Cholesterol, HDL; Ethanol, 64-17-5; Glycoproteins; Phosphatidylcholine-Sterol O-Acyltransferase, EC 2.3.1.43; Phospholipids; Triglycerides

Two experiments were conducted to determine apparent ileal DM and crude-protein (CP) digestibilities in rations fed to pigs. An evaluation was made of Cr2O3 and HCl-insoluble ash as digestive markers. In addition, the effects of body weight (BW) on apparent ileal DM and CP (N x 6.25) digestibilities were studied. In Expt 1, thirteen barrows averaging 35 kg BW were fitted with post-valve T-caecum (PVTC) cannulas to determine the apparent ileal DM and CP digestibilities of a wheat gluten-bran ration (B2) and a soyabean-meal ration (E1). Immediately after morning feeding ileal digesta samples were collected on an hourly basis for a total of 12 h. Subsequently, N and marker contents were determined in the samples. The postprandial patterns of N and Cr passage were more similar than those of N and HCl-insoluble ash. Therefore Cr2O3 is more suitable as a marker than HCl-insoluble ash. The apparent ileal CP digestibility coefficient of ration B2 derived using Cr2O3 as a marker was significantly (P < 0.05) higher by 0.018 compared with the value obtained using HCl-insoluble ash. The corresponding values for ration E2 obtained using Cr2O3 and HCl-insoluble ash were both 0.825. In Expt 2, apparent ileal DM and CP digestibilities were determined in eighteen rations using twelve barrows also fitted with PVTC cannulas (BW from 40 to 100 kg). The protein sources for these rations were from different groups of feedstuffs. In four and three of the rations apparent ileal DM and CP digestibilities respectively were significantly different (P < 0.05) when assessed using the two markers. The digestibility coefficients were not systematically higher or lower for either marker. Absolute differences were < 0.049 on average. Significant effects of live weight on apparent ileal CP digestibilities mere found.Chemicals/CAS: Biological Markers; Chromium Compounds; chromium oxide, 1308-38-9; Dietary Proteins; Nitrogen, 7727-37-9

1. The present study investigated the acute and chronic effect of dinner with alcoholic beverages on serum nitric oxide (NO) metabolites, namely nitrate and nitrite (NOx), in 11 healthy, non-smoking middle-aged men. 2. In a randomized, diet-controlled, cross-over trial, subjects consumed dinner with four glasses of red wine, beer, spirits (Dutch gin) or sparkling mineral water (control) for 3 weeks. At the end of each 3 week period, serum NOx concentrations were measured just before and 1, 5 and 13 h after dinner. 3. Serum NOx concentrations were approximately 50% higher 1 and 5 h after dinner with any beverage compared with just before dinner (P = 0.0001). At 1 h after dinner, the serum NOx concentration was approximately 11% lower after dinner with alcoholic beverages compared with concentrations observed after dinner with water (P = 0.01). The fasted serum NOx concentration (13 h after dinner) was similar to the preprandial concentration and there were no differences in serum NOx concentrations between the alcoholic beverages. 4. Food intake acutely and transiently increased serum NOx concentrations, an effect that was slightly attenuated if combined with alcoholic beverages. Chronic moderate alcohol consumption had no effect on serum NOx concentration.

This study examined postprandial plasma insulin and glucose responses after co-ingestion of an insulinotropic protein (Pro) hydrolysate with and without additional free leucine with a single bolus of carbohydrate (Cho). Male patients with long-standing Type 2 diabetes (n = 10) and healthy controls (n = 10) participated in 3 trials in which plasma glucose, insulin, and amino acid responses were determined after the ingestion of beverages of different composition (Cho: 0.7 g/kg carbohydrate, Cho+Pro: 0.7 g/kg carbohydrate with 0.3 g/kg protein hydrolysate, or Cho+Pro+Leu: 0.7 g/kg carbohydrate, 0.3 g/kg protein hydrolysate and 0.1 g/kg free leucine). Plasma insulin responses [expressed as area under the curve (AUC)] were 141 and 204% greater in patients with Type 2 diabetes and 66 and 221% greater in the controls in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P < 0.05). The concomitant plasma glucose responses were 15 and 12% lower in the patients with Type 2 diabetes and 92 and 97% lower in the control group in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P < 0.05). Plasma leucine concentrations correlated with the insulin response in all subjects (r = 0.43, P < 0.001). We conclude that co-ingestion of a protein hydrolysate with or without additional free leucine strongly augments the insulin response after ingestion of a single bolus of carbohydrate, thereby significantly reducing postprandial blood glucose excursions in patients with long-standing Type 2 diabetes. © 2006 American Society for Nutrition.

A large metabolomics study was performed on 600 plasma samples taken at four time points before and after a single intake of a high fat test meal by obese and lean subjects. All samples were analyzed by a liquid chromatography-mass spectrometry (LC-MS) lipidomic method for metabolic profiling. A pragmatic approach combining several well-established statistical methods was developed for processing this large data set in order to detect small differences in metabolic profiles in combination with a large biological variation. Such metabolomics studies require a careful analytical and statistical protocol. The strategy included data preprocessing, data analysis, and validation of statistical models. After several data preprocessing steps, partial least-squares discriminant analysis (PLS-DA) was used for finding biomarkers. To validate the found biomarkers statistically, the PLS-DA models were validated by means of a permutation test, biomarker models, and noninformative models. Univariate plots of potential biomarkers were used to obtain insight in up- or downregulation. The strategy proposed proved to be applicable for dealing with large-scale human metabolomics studies. © 2006 American Chemical Society.

Distension and chemosensitization of the stomach are insufficient to induce a ghrelin response, suggesting that postgastric feedback is required. This postgastric feedback may be regulated through insulin. We investigated the relation between gastric emptying rate and the postprandial ghrelin response as well as the role of insulin and other hormones possibly mediating this response. Fifteen healthy men [BMI 21.6 kg/m2 (SD 1.9), age 20.5 yr (SD 2.5)] were studied in a single-blind, crossover design. Subjects received two treatments separated by 1 wk: 1) a dairy breakfast in combination with a 3-h intravenous infusion of glucagon-like peptide-1 (GLP-1), which delays gastric emptying, and 2) a dairy breakfast in combination with a 3-h intravenous infusion of saline. Blood samples were drawn before breakfast and during the infusion. Postprandial ghrelin (total) responses were lower following the saline infusion compared with the GLP-1 infusion (P < 0.05). Acetaminophen concentrations, an indirect measurement of gastric emptying rate, were inversely correlated with total ghrelin concentrations (saline r = -0.76; 95% CI = -0.90, -0.49, GLP-1 r = -0.47; 95% CI = -0.76, -0.04). Ghrelin concentrations were only weakly correlated with insulin concentrations (saline r = -0.36; 95% CI = -0.69, 0.09; GLP- 1 r = -0.42; 95% CI = -0.73, 0.03), but strongly inversely correlated with GIP concentrations (saline r = -0.74; 95% CI= -0.89, -0.45; GLP-1 r = -0.63; 95% CI = -0.84, -0.27). In conclusion, our results support the hypothesis that ghrelin requires postgastric feedback, which may not be regulated through insulin. Conversely, our data suggest a role of glucose-dependent insulinotropic polypeptide in ghrelin secretion. Copyright © 2006 the American Physiological Society.

Background: A high plasma concentration of total homocysteine (tHcy) is associated with increased risk of cardiovascular disease. A high protein intake and hence a high intake of methionine-the sole dietary precursor of homocysteine-may raise plasma tHcy concentrations. Objectives: We studied whether high intake of protein increases plasma concentrations of tHcy in the fasting state and throughout the day. Design: We conducted a randomized, dietary controlled, crossover trial in 20 healthy men aged 18-44 y. For 8 d, men consumed a controlled low-protein diet enriched with either a protein supplement [high-protein diet (21% of energy as protein)] or an isocaloric amount of short-chain glucose polymers [low-protein diet (9% of energy as protein)]. After a 13-d washout period, treatments were reversed. On days 1 and 8 of each treatment period, blood was sampled before breakfast (fasting) and throughout the day. Results: Fasting tHcy concentrations did not differ significantly after the 1-wk high-protein and the 1-wk low-protein diets. The high-protein diet resulted in a significantly higher area under the 24-h homocysteine-by-time curves compared with the low-protein diet, both on day 1 (difference: 45.1 h · μmol/L; 95% CI: 35.3, 54.8 h · μmol/L; P < 0.0001) and on day 8 (difference: 24.7 h · μmol/L; 95% CI: 15.0, 34.5 h · μmol/L; P < 0.0001). Conclusions: A high-protein diet increases tHcy concentrations throughout the day but does not increase fasting tHcy concentrations. As previously shown, the extent of the tHcy increase is modified by the amino acid composition of the protein diet. The clinical relevance of this finding depends on whether high concentrations of tHcy-particularly postprandially-cause cardiovascular disease. © 2005 American Society for Clinical Nutrition.

Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma lipid levels independently of effects of apoE on lipid metabolism by comparing apolipoprotein E gene-deficient/apolipoprotein C-I gene-deficient (apoe -/-apoc1-/-), apoe-/-apoc +/-, and apoe-/-apoc1+/+ mice. The presence of the apoC-I gene-dose-dependently increased plasma cholesterol (+45%; P < 0.001) and triglycerides (TGs) (+137%; P < 0.001), both specific for VLDL. Whereas apoC-I did not affect intestinal [3H]TG absorption, it increased the production rate of hepatic VLDL-TG (+35%; P < 0.05) and VLDL-[ 35S]apoB (+39%; P < 0.01). In addition, apoC-I increased the postprandial TG response to an intragastric olive oil load (+120%; P < 0.05) and decreased the uptake of [3H]TG-derived FFAs from intravenously administered VLDL-like emulsion particles by gonadal and perirenal white adipose tissue (WAT) (-34% and -25%, respectively; P < 0.05). As LPL is the main enzyme involved in the clearance of TG-derived FFAs by WAT, and total postheparin plasma LPL levels were unaffected, these data demonstrate that endogenous apoC-I suffices to attenuate the lipolytic activity of LPL. Thus, we conclude that endogenous plasma apoC-I increases VLDL-total cholesterol and VLDL-TG dose-dependently in apoe-/- mice, resulting from increased VLDL particle production and LPL inhibition. Copyright © 2006 by the American Society for Biochemistry and Molecular Biology, Inc. Chemicals / CAS: cholesterol, 57-88-5; heparin, 37187-54-5, 8057-48-5, 8065-01-8, 9005-48-5; lipid, 66455-18-3; lipoprotein lipase, 83137-80-8, 9004-02-8; olive oil, 8001-25-0; Apolipoprotein C-I; Apolipoproteins C; Apolipoproteins E; Cholesterol, 57-88-5; Lipase, EC 3.1.1.3; Lipoprotein Lipase, EC 3.1.1.34; Lipoproteins, VLDL

ApoAV has been discovered recently as a novel modifier of triglyceride (TG) metabolism, but the pathways involved are currently unknown. To gain insight into the function of apoAV, adenovirus-mediated gene transfer of murine apoa5 to C57Bl/6 mice was employed. The injection of low doses of Ad-apoa5 (1-5 x 108 plaque-forming units/mouse) dose-dependently reduced plasma very low density lipoprotein (VLDL)-TG levels. First, we evaluated whether a reduced hepatic VLDL production contributed to the TG-lowering effect. Ad-apoa5 treatment dose-dependently diminished (29-37%) the VLDL-TG production rate without affecting VLDL particle production, suggesting that apoAV impairs the lipidation of apoB. Second, Ad-apoa5 treatment dose-dependently reduced (68-88%) the postprandial hypertriglyceridemia following an intragastric fat load, suggesting that apoAV also stimulates the lipoprotein lipase (LPL)-dependent clearance of TG-rich lipoproteins. Indeed, recombinant apoAV was found to dose-dependently stimulate LPL activity up to 2.3-fold in vitro. Accordingly, intravenously injected VLDL-like TG-rich emulsions were cleared at an accelerated rate concomitant with the increased uptake of emulsion TG-derived fatty acids by skeletal muscle and white adipose tissue in Ad-apoa5-treated mice. From these data, we conclude that apoAV is a potent stimulator of LPL activity. Thus, apoAV lowers plasma TG by both reducing the hepatic VLDL-TG production rate and by enhancing the lipolytic conversion of TG-rich lipoproteins. Chemicals / CAS: Apoa5 protein, mouse; Apolipoproteins; Lipids; Lipoprotein Lipase, EC 3.1.1.34; Lipoproteins; Lipoproteins, VLDL; Recombinant Proteins; Triglycerides; very low density lipoprotein triglyceride

Appetite suppressants may be one strategy in the fight against obesity. This study evaluated whether Korean pine nut free fatty acids (FFA) and triglycerides (TG) work as an appetite suppressant. Korean pine nut FFA were evaluated in STC-1 cell culture for their ability to increase cholecystokinin (CCK-8) secretion vs. several other dietary fatty acids from Italian stone pine nut fatty acids, oleic acid, linoleic acid, alpha-linolenic acid, and capric acid used as a control. At 50 μM concentration, Korean pine nut FFA produced the greatest amount of CCK-8 release (493 pg/ml) relative to the other fatty acids and control (46 pg/ml). A randomized, placebo-controlled, double-blind cross-over trial including 18 overweight post-menopausal women was performed. Subjects received capsules with 3 g Korean pine (Pinus koraiensis) nut FFA, 3 g pine nut TG or 3 g placebo (olive oil) in combination with a light breakfast. At 0, 30, 60, 90, 120, 180 and 240 minutes the gut hormones cholecystokinin (CCK-8), glucagon like peptide-1 (GLP-1), peptide YY (PYY) and ghrelin, and appetite sensations were measured. A wash-out period of one week separated each intervention day. CCK-8 was higher 30 min after pine nut FFA and 60 min after pine nut TG when compared to placebo (p < 0.01). GLP-1 was higher 60 min after pine nut FFA compared to placebo (p < 0.01). Over a period of 4 hours the total amount of plasma CCK-8 was 60% higher after pine nut FFA and 22% higher after pine nut TG than after placebo (p < 0.01). For GLP-1 this difference was 25% after pine nut FFA (P < 0.05). Ghrelin and PYY levels were not different between groups. The appetite sensation "prospective food intake" was 36% lower after pine nut FFA relative to placebo (P < 0.05). This study suggests that Korean pine nut may work as an appetite suppressant through an increasing effect on satiety hormones and a reduced prospective food intake. © 2008 Pasman et al; licensee BioMed Central Ltd.

Background: The most satiating macronutrient appears to be dietary protein. Few studies have investigated the effects of dietary protein on ghrelin secretion in humans. Objective: This study was designed to investigate whether a high-protein (HP) breakfast is more satiating than a high-carbohydrate breakfast (HC) through suppression of postprandial ghrelin concentrations or through other physiologic processes. Design: Fifteen healthy men were studied in a single-blind, crossover design. Blood samples and subjective measures of satiety were assessed frequently for 3 h after the consumption of 2 isocaloric breakfasts that differed in their protein and carbohydrate content (58.1% of energy from protein and 14.1% of energy from carbohydrate compared with19.3% of energy from protein and 47.3% of energy from carbohydrate). The gastric emptying rate was indirectly assessed with the acetaminophen absorption test. Results: The HP breakfast decreased postprandial ghrelin secretion more than did the HC breakfast (P < 0.01). Ghrelin concentrations were correlated with glucose-dependent insulinotropic polypeptide (r = -0.65; 95% CI: -0.85, -0.29) and glucagon concentrations (r = -0.47; 95% CI: -0.75, -0.03). Compared with the HC breakfast, the HP breakfast increased glucagon (P < 0.0001) and cholecystokinin (P < 0.01), tended to increase glucose-dependent insulinotropic polypeptide (P = 0.07) and glucagon-like peptide 1 (P = 0.10), and decreased the gastric emptying rate (P < 0.0001). Appetite ratings were not significantly different between the 2 treatments, and the HP breakfast did not significantly affect ad libitum energy intake. Conclusions: The HP breakfast decreased postprandial ghrelin concentrations more strongly over time than did the HC breakfast. High associations between ghrelin and glucose-dependent insulinotropic polypeptide and glucagon suggest that stimulation of these peptides may mediate the postprandial ghrelin response. The HP breakfast also reduced gastric emptying, probably through increased secretion of cholecystokinin and glucagon-like peptide 1. © 2006 American Society for Nutrition.

Background: Ghrelin plays an important role in the regulation of food intake. Little is known about how ghrelin concentrations are modified by dietary factors. Objective: We examined the effects of both amount and type of carbohydrate on ghrelin concentrations and all correlations among the variables ghrelin, glucose, insulin, leptin, and all 4 subjective measures of appetite. Design: Twenty healthy nonobese men were studied in a double-blind, randomized, crossover design. Subjective measures of appetite and concentrations of ghrelin, glucose, insulin, and leptin were frequently assessed for 4 h after liquid breakfast meals differing in energy content and carbohydrate structure-ie, water, low-calorie (LC) meal, high-calorie simple carbohydrate (HC-SC) meal, and high-calorie complex carbohydrate (HC-CC) meal. Results: Ghrelin concentrations decreased after the HC-SC breakfast by 41%, after the HC-CC breakfast by 33%, and after the LC breakfast by 24%. No significant differences in ghrelin concentration among the 3 breakfasts were observed until 120 min. Ghrelin concentrations were correlated with subjective measures of hunger (r = 0.51) and fullness (r = -0.44). The percentage decrease in ghrelin between 0 and 30 min was inversely correlated with the percentage increases in insulin (r = -0.76) and glucose (r= -0.79) but not with changes in leptin (r = 0.10). The percentage changes in ghrelin concentrations between 30 and 180 min were correlated with the percentage changes in insulin (r= -0.53) and leptin (r= -0.47) but not with changes in glucose (r = 0.22). Conclusion: The results support the hypothesis that ghrelin requires postgastric feedback, which may be regulated through insulin. © 2005 American Society for Clinical Nutrition.

Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified among the most responsive plasma metabolites in the postprandial state. We here describe this response to different dietary challenges and report on key determinants linked to its interindividual variability. Healthy men and women (n = 72, 62 ± 8 yr, mean ± SE) were enrolled into a 12-wk weight loss intervention. All subjects underwent an oral glucose tolerance test and a mixed-meal tolerance test before and after the intervention. BA were quantified in plasma by liquid chromatography-tandem mass spectrometry combined with whole genome exome sequencing and fecal microbiota profiling. Considering the average response of all 72 subjects, no effect of the successful weight loss intervention was found on plasma BA profiles. Fasting and postprandial BA profiles revealed high interindividual variability, and three main patterns in postprandial BA response were identified using multivariate analysis. Although the women enrolled were postmeno-pausal, effects of sex difference in BA response were evident. Exome data revealed the contribution of preselected genes to the observed interindividual variability. In particular, a variant in the SLCO1A2 gene, encoding the small intestinal BA transporter organic anion-transporting polypeptide-1A2 (OATP1A2), was associated with delayed postprandial BA increases. Fecal microbiota analysis did not reveal evidence for a significant influence of bacterial diversity and/or composition on plasma BA profiles. The analysis of plasma BA profiles in response to two different dietary challenges revealed a high interindividual variability, which was mainly determined by genetics and sex difference of host with minimal effects of the microbiota. NEW & NOTEWORTHY Considering the average response of all 72 subjects, no effect of the successful weight loss intervention was found on plasma bile acid (BA) profiles. Despite high interindividual variability, three main patterns in postprandial BA response were identified using multivariate analysis. A variant in the SLCO1A2 gene, encoding the small intestinal BA transporter organic anion-transporting polypeptide-1A2 (OATP1A2), was associated with delayed postprandial BA increases in response to both the oral glucose tolerance test and the mixed-meal tolerance test. © 2017, American Physiological Society. All rights reserved. Chemicals/CAS: chenodeoxycholic acid, 474-25-9; cholic acid, 32500-01-9, 361-09-1, 81-25-4; deoxycholic acid, 83-44-3; glycine, 56-40-6, 6000-43-7, 6000-44-8; glycochenodeoxycholic acid, 640-79-9; glycocholic acid, 475-31-0; glycodeoxycholic acid, 16409-34-0, 360-65-6; taurine, 107-35-7; taurochenodeoxycholic acid, 516-35-8; taurocholic acid, 145-42-6, 59005-70-8, 81-24-3; taurodeoxycholic acid, 1180-95-6, 516-50-7; tauroursodeoxycholic acid, 14605-22-2; ursodeoxycholic acid, 128-13-2, 2898-95-5; Bile Acids and Salts

Objective - The use of the HIV protease inhibitor ritonavir (RTV) is frequently associated with hypertriglyceridemia and lipodystrophy. The aim of our study was to determine the mechanism underlying the observed hypertriglyceridemia. Methods and Results - Feeding female APOE*3-Leiden transgenic mice a Western-type diet supplemented with RTV (35 mg/kg per day) for 2 weeks resulted in a 2-fold increase in fasting plasma triglyceride (TG) levels, which was specific for very low-density lipoprotein (VLDL). RTV did not change the hepatic VLDL-TG production. Instead, RTV did increase the postprandial TG response to an oral fat load (area under the curve, 25.5±12.1 versus 13.8±6.8 mmol/L per hour in controls; P<0.05). Likewise, RTV hampered the plasma clearance of intravenously injected glycerol tri[3H]oleate-labeled VLDL-like emulsion particles (half time, 19.3±10.5 versus 5.0±1.3 minutes in controls; P<0.05) associated with a decrease of 44% in plasma lipoprotein lipase activity. Accordingly, RTV decreased the uptake of TG-derived fatty acids (FAs) into adipose tissue, as well as the uptake of albumin-bound FA. Conclusions - We conclude that RTV causes hypertriglyceridemia via decreased lipoprotein lipase-mediated clearance of VLDL-TG. In addition, RTV specifically impairs the uptake of FA in adipose tissue, which may contribute to the lipodystrophy that is frequently observed in HIV-infected subjects on antiretroviral therapy. © 2005 American Heart Association, Inc. Chemicals / CAS: lipoprotein lipase, 83137-80-8, 9004-02-8; proteinase inhibitor, 37205-61-1; ritonavir, 155213-67-5; triolein, 122-32-7; heparin, 37187-54-5, 8057-48-5, 8065-01-8, 9005-48-5; tritium, 10028-17-8; Anticoagulants; apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins E; Cholesterol, VLDL; Emulsions; Fatty Acids; Heparin, 9005-49-6; HIV Protease Inhibitors; Lipoprotein Lipase, EC 3.1.1.34; Ritonavir; Triglycerides; Triolein, 122-32-7; Tritium, 10028-17-8