PubMed Health⌕ Search

Biomedical subjects

M Senft

Publications and source records attributed to M Senft.

At least 19 recordsLinked to original sources

Dietary cholesterol is secreted in intestinally derived chylomicrons during several subsequent postprandial phases in healthy humans.

BACKGROUND: The process of intestinal absorption and chylomicron resecretion of dietary cholesterol in humans is poorly understood. OBJECTIVE: The present study aimed to test the hypothesis that dietary cholesterol ingested during a given meal is resecreted into chylomicrons (and plasma) during several subsequent postprandial periods. DESIGN: Seven healthy subjects ingested 3 comparable mixed test meals (at 0, 8, and 24 h) containing a given amount of fat (49 g) and cholesterol (157 mg); blood samples were taken 3 and 6 h after each test meal and 48 and 72 h after the beginning of the experiment. Heptadeuterated dietary cholesterol was present in the first test meal only, enabling its specific determination with use of gas chromatography-mass spectrometry. Chylomicrons, LDL, and HDL were isolated and lipids were quantified. RESULTS: In apolipoprotein B-48-containing chylomicrons, deuterated cholesterol concentrations were moderate after the first meal (1.3 x 10(-4) mmol/L), reached a maximum after the second meal (2.4 x 10(-4) mmol/L), and were still elevated after the third meal (1.7 x 10(-4) mmol/L). In plasma, LDL and HDL cholesterol enrichment in deuterated cholesterol was lower than in chylomicrons and plateaued after 24--48 h. Estimates of newly secreted exogenous deuterated cholesterol in chylomicrons indicate that 30.7%, 55.2%, and 14.1% of the total was secreted after the first, second, and third meals, respectively. CONCLUSION: Ingested dietary cholesterol is secreted by the small intestine in chylomicrons into the circulation during > or =3 subsequent postprandial periods in healthy humans. This likely results from a complex multistep intestinal processing of cholesterol with dietary fat as a driving force.

Adult↗

Processing of vitamin A and E in the human gastrointestinal tract.

We aimed to provide basic data on the processing of vitamin A and E in the human gastrointestinal tract and to assess whether the size of emulsion fat globules affects the bioavailability of these vitamins. Eight healthy men received intragastrically two lipid formulas differing in their fat-globule median diameter (0.7 vs. 10. 1 microm. Formulas provided 28 mg vitamin A as retinyl palmitate and 440 mg vitamin E as all-rac alpha-tocopherol. Vitamins were measured in gastric and duodenal aspirates, as well as in chylomicrons, during the postprandial period. The gastric emptying rate of lipids and vitamin A and E was similar. The free retinol/total vitamin A ratio was not significantly modified in the stomach, whereas it was dramatically increased in the duodenum. The proportion of ingested lipid and vitamins was very similar in the duodenal content. The chylomicron response of lipids and vitamins was not significantly different between the two emulsions. Our main conclusions are as follows: 1) there is no significant metabolism of vitamin A and E in the human stomach, 2) the enzyme(s) present in the duodenal lumen is significantly involved in the hydrolysis of retinyl esters, and 3) the size of emulsion fat globules has no major effect on the overall absorption of vitamin A and E.

Adult↗

Acute hyperinsulinism modulates plasma apolipoprotein B-48 triglyceride-rich lipoproteins in healthy subjects during the postprandial period.

The role of postprandial insulin in the regulation of postprandial lipid metabolism is still poorly understood. The roles of hyperinsulinemia and insulin resistance in the alteration of postprandial lipid metabolism are not clear either. To improve knowledge in this area, we submitted healthy men to acute hyperinsulinemia in two different ways. In the first study, we compared in 10 men the effects of four isolipidic test meals that induce different degrees of hyperinsulinemia on postprandial lipid metabolism. Three different carbohydrate sources were compared according to their glycemic indexes (GIs; 35, 75, and 100 for white kidney bean, spaghetti, and white bread test meals, respectively); the fourth test meal did not contain any carbohydrates. Postprandial plasma insulin levels were proportional to the GIs (maximal plasma insulin concentrations: 113 +/- 16 to 266 +/- 36 pmol/l). We found a strong positive correlation during the 6-h postprandial period between apolipoprotein (apo) B-48 plasma concentration and insulin plasma concentration (r2 = 0.70; P = 0.0001). In a second study, 5 of the 10 subjects again ingested the carbohydrate-free meal, but during a 3-h hyperinsulinemic- (550 +/- 145 pmol/l plasma insulin) euglycemic (5.5 +/- 0.8 mmol/l plasma glucose) clamp. A biphasic response was observed with markedly reduced levels of plasma apoB-48 during insulin infusion, followed by a late accumulation of plasma apoB-48 and triglycerides. Overall, the data obtained showed that portal and peripheral hyperinsulinism delays and exacerbates postprandial accumulation of intestinally derived chylomicrons in plasma and thus is involved in the regulation of apoB-48-triglyceride-rich lipoprotein metabolism, in the absence of insulin-resistance syndrome.

Acute Disease↗

Chronically gorging v. nibbling fat and cholesterol increases postprandial lipaemia and atheroma deposition in the New Zealand white rabbit.

In the present study, we compared the effects of nibbling and gorging on postprandial lipaemia and lipoproteins, hepatic lipid uptake and atheroma deposition. New Zealand White rabbits were fed on a low-fat (LF) control diet or a peanut oil- (10 g/d) and cholesterol- (0.5 g/d) enriched (HF) diet with the fat and cholesterol components given either by nibbling (HF-N) or gorging (HF-G). After 4 and 8 weeks, rabbits were given a test meal, which was either nibbled or taken as a bolus. The LF diet did not noticeably alter postprantial lipid variables. Triacylglycerol levels, 0-35 h lipid responses and plasma accumulation of dietary lipids were significantly higher in the HF-G group than in the HF-N group, despite higher post-heparin plasma lipase activities. Furthermore, as studied on cultured isolated hepatocytes, the higher the rate of supply of triacylglycerol- and cholesterol-rich lipoproteins (TCRL), the lower the rate of lipid uptake and bile salt secretion. Atheroma deposition was significantly increased by gorging the HF diet and was correlated with levels of most postprandial lipid variables. We conclude that gorging v. nibbling a fat and cholesterol-enriched diet exacerbates postprandial lipaemia by reducing the rate of TCRL clearance and favours atheroma deposition.

Animals↗

Acute ingestion of different dietary fatty acid species modulates postprandial lipid responses in New Zealand white rabbits.

Although several investigations have linked the degree of fatty acid saturation to plasma lipid responses in the postprandial state, further evaluation is necessary. In this study, we compared the effect of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids on postprandial lipid metabolism using complementary in vivo and in vitro approaches. Fat (10 g) cholesterol (0.5 g) test meals that provided either lard (SFA), olive oil (MUFA), or sunflower oil (PUFA) were ingested by chow-fed New Zealand white rabbits (n = 8). In addition, hepatic uptake of triglyceride-cholesterol-rich lipoproteins (TCRL) isolated from rabbits chronically ingesting SFA, MUFA, or PUFA diets was measured using freshly isolated chow-fed rabbit hepatocytes. Whatever dietary fatty acids ingested, postprandial triglyceridemia and occurrence of radiolabelled dietary lipids in plasma were not markedly different. Conversely, SFA induced higher postprandial cholesterolemia and phospholipemia than MUFA (P < 0.05) whereas PUFA prevented postprandial cholesterol increase. TCRL disappearance from cultured liver cell media was delayed with SFA-rich TCRL and faster with PUFA whereas MUFA-rich TCRL showed an intermediate figure. From these data, we conclude that SFA, MUFA, and PUFA elicited different postprandial plasma and lipoprotein lipid responses. The fatty acid composition of TCRL had a major impact on their subsequent metabolism, especially uptake by cultured hepatocytes. The SFA-induced hypercholesterolemia could be related to an altered hepatic uptake whereas a faster clearance and hepatic uptake could explain the cholesterol-lowering effect of PUFA in rabbits. MUFA, like PUFA, accelerate uptake by hepatocytes but favor cholesterol ester enrichment of TCRL.

Journal Article↗

Digestion and absorption of 2 fat emulsions with different droplet sizes in the human digestive tract.

BACKGROUND: The extent of fat emulsification affects the activity of digestive lipases in vitro and may govern digestion and absorption of dietary fat. OBJECTIVE: We investigated the effect of the fat globule size of 2 enteral emulsions on fat digestion and assimilation in humans. DESIGN: Healthy subjects received intragastrically a coarse (10 microm) and a fine (0.7 microm) lipid emulsion of identical composition in random order. Gastric and duodenal aspirates were collected throughout digestion to measure changes in fat droplet size, gastric and pancreatic lipase activities, and fat digestion. Blood lipids were measured postprandially for fat assimilation. RESULTS: Despite an increase in droplet size in the stomach (2.75-6.20 microm), the fine emulsion retained droplets of smaller size and its lipolysis was greater than that of the coarse emulsion (36.5% compared with 15.8%; P < 0.05). In the duodenum, lipolysis of the fine emulsion was on the whole higher (73.3% compared with 46.3%). The overall 0-7-h plasma and chylomicron responses given by the areas under the curve were not significantly different between the emulsions, but the triacylglycerol peak was delayed with the fine emulsion (3 h 56 min compared with 2 h 50 min). CONCLUSIONS: Fat emulsions behave differently in the digestive tract depending on their initial physicochemical properties. A lower initial fat droplet size facilitates fat digestion by gastric lipase in the stomach and duodenal lipolysis. Overall fat assimilation in healthy subjects is not affected by differences in initial droplet size because of efficient fat digestion by pancreatic lipase in the small intestine. Nevertheless, these new observations could be of interest in the enteral nutrition of subjects suffering from pancreatic insufficiency.

Absorption↗

Postprandial lipaemia is exacerbated in fat-cholesterol-fed rabbits: relationship to atheroma deposition.

The aim of the present study was to evaluate the links between chronic fat-cholesterol intake, postprandial lipaemia and atherogenesis in New Zealand White rabbits. Adult rabbits were fed on either a low-fat control diet (LF) or a high-fat, high-cholesterol diet (HF). Rabbits received a test meal containing [3H]cholesterol and [14C]triolein on days 0 and 63 for the LF group and days 14, 28, 42, 63 and 84 for the HF group. Blood was collected 24 h post-absorptively and 10, 24, 34 and 48 h after test-meal intake. Post-absorptive as well as postprandial lipoproteins and lipaemia were not modified in the LF rabbits, who did not show any atheroma deposition on day 119. In HF rabbits, postprandial plasma triacylglycerols peaked 24-34 h after meal intake. The 0-48 h areas under the curves of triacylglycerol and triacylglycerol-rich lipoproteins (TRL) steadily increased with time of chronic lipid feeding with values significantly higher than those in the LF rabbits. The postprandial plasma and TRL concentrations of dietary radiolabelled lipids were significantly higher in HF than LF rabbits. Post-heparin lipoprotein lipase (EC 3.1.1.34) and hepatic lipase (EC 3.1.1.3) activities were twofold higher in HF rabbits than in LF rabbits at day 105. In HF rabbits, a marked atheroma plaque deposition in the aorta was observed (30.9 (SE 3.9) % of total surface). The extent of atheroma deposition was positively correlated to the postprandial responses of plasma total triacylglycerols and dietary-derived lipids as well as total cholesterol and dietary-derived cholesterol in HF rabbits. In conclusion, chronic ingestion of a HF diet led to marked increases in postprandial lipaemia and TRL particles, and atheroma deposition.

Animals↗

Postprandial lipemia in relation to sterol and fat excretion in ileostomy subjects given oat-bran and wheat test meals.

To investigate the mechanisms behind the serum cholesterol-lowering effect of oat fiber, we simultaneously measured postprandial lipid responses, serum lathosterol concentrations, and small bowel excretion of fat and sterols in ileostomy subjects given test meals high or low in oat fiber. Six ileostomy subjects (three women and three men) were served an oat-bran test meal (OB; 16.3 g fiber) and a wheat test meal (6.3 g fiber) in random order. After the postprandial 7-h period, a controlled, low-fat, cholesterol-free diet was served and ileostomy effluent was sampled throughout the 24-h period. Bile acid and fat excretion (24 h) increased by 93% and 146%, respectively (P < 0.05), and total and endogenous cholesterol excretion decreased by 14% and 19%, respectively (P < 0.05), after the OB test meal. The change in hepatic cholesterol synthesis was strongly related to the change in bile acid excretion (Spearman r = 0.89, P < 0.02). The postprandial chylomicron lipid concentration tended to be lower after the OB test meal (-43% for cholesterol, P = 0.07) whereas there was no difference in cholesterol absorption measured by isotope in five subjects. The main effect of the viscous oat beta-glucan seems to be related to increased bile acid excretion and subsequent changes in synthesis and endogenous excretion of cholesterol. An additional effect may have been a delay in the micellar lipid solubilization process and a consequent reduction in the secretion of chylomicrons into the circulation.

Adult↗

Effects of lowering fat and increasing dietary fiber on fasting and postprandial plasma lipids in hypercholesterolemic subjects consuming a mixed Mediterranean-Western diet.

The aim of this study was to evaluate the cholesterol-lowering effects of reducing fat and increasing or not increasing dietary fiber in subjects consuming a mixed Mediterranean-Western diet. Thirty-one free-living, mildly hypercholesterolemic subjects were randomly allocated to two groups. Subjects in both groups first shifted for 4 wk to a low-fat, low-fiber diet (LFLFD). For an additional 4-wk period, subjects in group 1 continued consuming the LFLFD whereas subjects in group 2 consumed a low-fat, high-fiber diet (LFHFD). Most dietary fatty acids were monounsaturated (38-41%) and fibers, when provided (up to 35 g/d), came from unrefined cereals, legumes, and soluble-fiber-enriched ready-to-eat cereals. After period 1 of the LFLFD, mean serum and low-density-lipoprotein (LDL)-cholesterol concentrations of subjects in groups 1 (-12.5% and -15.5%, respectively) and 2 (-10.5% and -15.5%, respectively) decreased significantly from baseline (P < 0.05). After period 2, mean serum and LDL-cholesterol concentrations of subjects consuming the LFLFD (group 1) were still lower (by 8.8% and 9.2%, respectively, from baseline) whereas in subjects consuming the LFHFD (group 2) these values decreased further to significantly lower values (14.2% and 17.6% from baseline, respectively). Fasting high-density-lipoprotein (HDL) cholesterol, apolipoprotein A-I, glycemia, and insulinemia did not change significantly. In seven men, postprandial lipemia transiently increased more after a breakfast test meal at the completion of the LFHFD period than after the LFLFD period. In conclusion, an LFHFD more comparable with the traditional Mediterranean diet may improve the dietary management of moderate hypercholesterolemia.

Adult↗

Physicochemical characteristics of emulsions during fat digestion in human stomach and duodenum.

Seven fasting subjects were fitted with nasogastric and nasoduodenal tubes and received intragastrically a coarsely emulsified test meal. Gastric and duodenal aspirates were collected after 1, 2, 3, and 4 h. In the duodenum, most lipids (> 90%) were present as emulsified droplets 1-100 microns in size. Large droplets and unemulsified material present in the test meal (> 100 micron) disappeared, whereas smaller droplets (1-50 microns) were generated after 1 h of digestion. Thus the median lipid droplet diameter significantly decreased (19.6 vs. 56.5 microns in the test meal) and the droplet surface area significantly increased (1.58 vs. 0.70 micron2/g fat). Intermediate droplet diameters were 34.3, 46.3, and 27.6 microns after 2, 3, and 4 h, respectively. In the stomach, a comparable emulsion particle size pattern was observed, with median droplet diameters of 17.2, 37.9, 52.4, and 41.6 microns after 1, 2, 3, and 4 h, respectively. However, the extent of triglyceride hydrolysis was much lower in the stomach (6-16%) than in the duodenum (42-45%), where small droplets were enriched in lipolytic products, cholesterol, and phospholipids. The present findings show for the first time that most dietary lipids are present in the human duodenum as emulsified droplets 1-50 microns in size and that no further marked emulsification of dietary fat occurs in the duodenum compared with the stomach.

Adult↗

Chronic oat bran intake alters postprandial lipemia and lipoproteins in healthy adults.

This study evaluates the possible interaction between chronic oat bran intake and the postmeal metabolic response. Six normolipidemic men consumed three different diets for 14 d, at the end of which they consumed a test meal. The diets were C (control), basal low-fiber diet (15.6 g fiber/d) and a low-fiber (2.8 g fiber) test meal; OB (oat bran), basal low-fiber diet and a 40-g oat bran-enriched test meal (12.8 g fiber); and OB-A (oat bran-adaptation), 14-d oat bran (40 g/d) supplemented diet (23.8 g fiber/d) and an oat bran test meal (12.8 g fiber). The diets were fed in a random order. Fasting and postmeal blood samples were obtained for 7 h and lipoproteins were isolated. Adding oat bran to the test meals markedly reduced the postmeal insulin rise (P < 0.05). Compared with the low-fiber control diet, the effects elicited postprandially by adding oat bran to a single meal were enhanced after 14 d of oat bran feeding, ie, increased plasma triglycerides, phospholipids, and free cholesterol; decreased plasma esterified cholesterol; increased chylomicron and small-sized triglyceride-rich lipoprotein triglycerides; increased LDL and HDL free cholesterol; and decreased HDL esterified cholesterol. Thus, chronic oat bran feeding alters the postmeal response in human subjects.

Adult↗

Characterization of emulsions and lipolysis of dietary lipids in the human stomach.

Fasting subjects were intragastrically intubated and received a coarsely emulsified test meal. Gastric aspirates were collected after 1, 2, 3, and 4 h. During digestion in the stomach, unemulsified lipids (> or = 100 microns) represented a minor fraction. A significant amount of the large 70- to 100-microns lipid droplets disappeared, and fine 1- to 10-microns droplets were generated. The median lipid droplet diameter significantly decreased (21.9 vs. 52.9 microns) after 1 h and kept intermediate values for longer periods of time. The emulsion surface area was 100-120 m2/l and was basically provided by 1- to 100-microns droplets. Lipolysis catalyzed by gastric lipase primarily occurred within the first hour of digestion (11.9%). Smaller droplets were enriched in triglyceride lipolytic products. The free fatty acid concentrations were in the range of 5.6-8.2 mM over 1-4 h. The present finding demonstrates for the first time that in the human stomach most dietary lipids are present in the form of emulsified droplets, in the range of 20-40 microns, and that gastric lipolysis can help to increase emulsification in the stomach.

Dietary Fats↗

Mechanisms of action in the liver of crilvastatin, a new hydroxymethylglutaryl-coenzyme A reductase inhibitor.

Crilvastatin is a drug from the pyrrolidone family that had been shown to induce non-competitive inhibition of rat hydroxymethylglutaryl-coenzyme A reductase activity in vitro. The aim of this study was to evaluate the activity of crilvastatin on the hepatic metabolism of cholesterol in rats. Crilvastatin increased low density lipoprotein (LDL)-cholesterol uptake by the liver more than high density lipoprotein (HDL) uptake, thus increasing by up 30% the clearance of excess plasma cholesterol. In normolipidemic rats, crilvastatin significantly enhanced acyl coenzyme A:cholesterol acyl transferase and cholesterol 7 alpha-hydroxylase activity. In rats with a previous high cholesterolemia, crilvastatin also enhanced cholesterol 7 alpha-hydroxylase activity and did not increase liver acyl coenzyme A:cholesterol acyl transferase activity. These findings suggest that a drug such as crilvastatin could have a hypocholesterolemic effect by a mechanism other than the sole inhibition of cholesterol synthesis, possibly by stimulating cholesterol and bile salt secretion via the biliary tract in previously hypercholesterolemic rats.

Animals↗

The influence of supportive nutritional therapy via percutaneous endoscopically guided gastrostomy on the quality of life of cancer patients.

Between April 1987 and May 1990 a total of 212 consecutive patients with tumours in the head and neck region were admitted to a prospective study comparing planned prospective enteral nutrition via percutaneous endoscopically guided gastrostomy (PEG; n = 47) and oral nutrition (n = 134). The nutritional status (anthropometric and laboratory chemical parameters) and the quality-of-life index according to Padilla et al. [Res Nurs Health 6:117-126 (1983)] were determined prior to radiotherapy, 2, 4, 6 weeks later during radiotherapy and 6, 12 and 18 weeks after completion of radiotherapy. The quality-of-life score of the orally nourished patients decreased quickly during radiotherapy and improved only slowly afterwards. Although PEG patients had a worse starting score, their quality-of-life index did not deteriorate during therapy (statistically significant difference between the two groups). The same applies to the nutritional status. These results show that an early and constant enteral nutrition by PEG can stabilize the nutritional state and the quality of life of patients with tumours of the head and neck area during radiotherapy.

Adult↗

Effects of pea and soybean fibre on postprandial lipaemia and lipoproteins in healthy adults.

To evaluate some possible mechanisms whereby total dietary fibre (TDF) may affect lipid metabolism in humans, six normolipidaemic males ingested on separate days a low-fibre test meal (2.8 g TDF) containing 70 g fat and 756 mg cholesterol, enriched with 10 g TDF in the form of either pea fibre or soybean fibre. Fasting and post-meal blood samples were obtained for 7 h and chylomicrons (CM) were isolated. Lipoproteins (VLDL+CM remnants, LDL, HDL) were isolated from the baseline samples and the samples of the 2-3 h triglyceride peaks. As compared to the postprandial response given by the control low-fibre test meal, adding fibre induced no change in serum glucose, insulin or Apo A1 and Apo B variations. The serum triglyceride response was not altered by adding fibres but the 2-3 h chylomicron triglyceride rise was increased (P < or = 0.05) by soybean fibre. VLDL+CM remnants, LDL and HDL triglyceride variations were unchanged with fibres. Cholesterolaemia decreased postprandially for 6 h, and was further lowered in the presence of pea fibre. This resulted from a marked decrease in serum esterified cholesterol. The chylomicron cholesterol and phospholipid rise was lowered in the presence of either fibre. The postprandial changes in the free cholesterol concentrations of the various lipoprotein classes were not altered by fibre whereas changes from baseline in esterified cholesterol concentrations were reduced by soybean fibre in LDL and amplified by soybean and pea fibres in HDL. The results obtained show that dietary fibre present in legumes may alter postprandial lipaemia and lipoproteins in humans to a variable extent. These effects could be related to some long-term metabolic effects.

Adult↗

Effects of oat bran, rice bran, wheat fiber, and wheat germ on postprandial lipemia in healthy adults.

Six normolipidemic males ingested on separate days a low-fiber test meal [2.8 g dietary fiber (TDF)] containing 70 g fat and 756 mg cholesterol, enriched or not with 10 g TDF as oat bran, rice bran, or wheat fiber or 4.2 g TDF as wheat germ. Fasting and postmeal blood samples were obtained for 7 h and chylomicrons were isolated. Adding fibers to the test meal induced no change in serum glucose or insulin responses. The serum triglyceride response was lower (P less than or equal to 0.05) in the presence of oat bran, wheat fiber, or wheat germ and chylomicron triglycerides were reduced with wheat fiber. All fiber sources reduced chylomicron cholesterol. Cholesterolemia decreased postprandially for 6 h and was further lowered in the presence of oat bran. Serum apolipoprotein (apo) A-1 and apo B concentrations were not affected. Thus, dietary fibers from cereals may reduce postprandial lipemia in humans to a variable extent.

Adult↗