Postprandial Serum Triacylglycerol Research Articles

Effects of Dietary Blueberry (Vaccinium ashei Reade) Leaves on Mildly Postprandial Hypertriglyceridemia.

Prevention of postprandial hypertriglyceridemia is an important consideration for reducing the risk of developing cardiovascular disease. While blueberry fruits have been reported to ameliorate lipid metabolism in humans, there are only few research reports on the effects of blueberry leaves (BL). Here, we investigated the efficacy of BL on postprandial hyperlipidemia in subjects with high fasting triacylglycerol (TG) concentrations. Randomized, double-blind, cross-over design study was conducted. The subjects consumed a BL containing beverage or a placebo beverage before a fat-enriched test meal. Blood samples were collected prior to and 1, 2, 3, 4, and 5 hours after consuming the test beverage. The postprandial serum TG and remnant-like particle cholesterol (RLP-C) concentrations were significantly lower in the BL beverage compared with those in the placebo beverage. Additionally, BL was more effective in subjects with high fasting ghrelin with gastric emptying function. In current study, fasting ghrelin correlated with the increase in postprandial serum TG, suggesting that BL ameliorates hypertriglyceridemia through delayed gastric emptying. In conclusion, this pilot study suggests that BL may be useful as an early dietary therapy for treating postprandial hyperlipidemia.

Rat Small Intestinal Mucosal Epithelial Cells Absorb Dietary 1,3-Diacylglycerol Via Phosphatidic Acid Pathways.

Compared with triacylglycerol (TAG), dietary 1,3-diacylglycerol (1,3-DAG) is associated with reduced serum lipid and glucose levels. We investigated the metabolism of 1,3-DAG by assaying its intermediate metabolites during digestion and absorption in the rat small intestine. After gavage with TAG emulsion, TAG was digested mainly to 2-monoacylglycerol (2-MAG) and unesterified fatty acid (FFA) in the rat small intestinal lumen. 2-MAG was directly absorbed into the small intestinal epithelial cells and esterified to 1,2(2,3)-DAG, and further esterified to TAG. After gavage with 1,3-DAG emulsion, 1,3-DAG was digested mainly to 1(3)-MAG and FFA in the rat small intestinal lumen with subsequent significant increase of 1-MAG and 1,3-DAG concentrations in small intestinal mucosal epithelial cells, and the 2-MAG, 1,2(2,3)-DAG, and TAG concentrations in mucosal epithelial cells were not significantly different after 1,3-DAG than after TAG gavage, suggesting that the metabolic pathway of 1,3-DAG is different from that of TAG. In intestinal mucosal epithelial cells, we further assayed enzyme levels and gene expression of proteins in the phosphatidic acid (PtdOH) pathway. The glycerol kinase, phosphatidate phosphatase, and diacylglycerol acyltransferase-2 expression and the relative expression of mRNA of enzymes were significantly increased in the 1,3-DAG group compared with the TAG group, suggesting that TAG synthesis from dietary 1,3-DAG was mainly via PtdOH pathways, which may partially account for the effect of dietary DAG on postprandial serum TAG.

Lactobacillus gasseri SBT2055 reduces postprandial and fasting serum non-esterified fatty acid levels in Japanese hypertriacylglycerolemic subjects

BackgroundLactobacillus gasseri SBT2055 (LG2055) inhibits dietary fat absorption in rats and exerts preventive effects on abdominal adiposity in rats and humans. The present study aimed to evaluate the effects of LG2055 on postprandial serum lipid responses in Japanese subjects with hypertriacylglycerolemia after the intake of oral fat-loading test (OFLT) meals.MethodsWe conducted a single-blind, placebo-controlled, within-subject, repeated-measure intervention trial. Twenty subjects initially ingested the fermented milk (FM) without LG2055 for 4 weeks (control FM period), followed by a 4-week washout period, and then consumed FM containing LG2055 for 4 weeks (active FM period). The subjects were asked to consume FM at 200 g/day. At the end of each 4-week period, an 8-h OFLT was conducted. Blood samples were collected at fasting and every hour for 8 h after OFLT meal intake. Thereafter, postprandial serum non-esterified fatty acid (NEFA) and triacylglycerol (TAG) levels and fasting blood parameters were measured.ResultsThe OFLT showed that the postprandial serum NEFA levels from 120 to 480 min and the postprandial serum TAG level at 120 min in the active FM period were significantly (P < 0.05) lower than those in the control FM period. The fasting serum NEFA level in the active FM period significantly (P < 0.001) decreased at week 4 from the initial period compared with the control FM period.ConclusionsThe consumption of probiotic LG2055 reduced postprandial and fasting serum NEFA levels, suggesting its possible contribution to the reduction of the risk for obesity and type 2 diabetes mellitus.Trial registrationUMIN000011605

Diacylglycerol acyltransferase 1 inhibition with AZD7687 alters lipid handling and hormone secretion in the gut with intolerable side effects: a randomized clinical trial

Inhibition of diacylglycerol acyltransferase 1 (DGAT1) is a potential treatment modality for patients with type 2 diabetes mellitus and obesity, based on preclinical data suggesting it is associated with insulin sensitization and weight loss. This randomized, placebo-controlled, phase 1 study in 62 overweight or obese men explored the effects and tolerability of AZD7687, a reversible and selective DGAT1 inhibitor. Multiple doses of AZD7687 (1, 2.5, 5, 10 and 20 mg/day, n = 6 or n = 12 for each) or placebo (n = 20) were administered for 1 week. Postprandial serum triacylglycerol (TAG) was measured for 8 h after a standardized 45% fat meal. Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were measured and a paracetamol challenge was performed to assess gastric emptying. Dose-dependent reductions in postprandial serum TAG were demonstrated with AZD7687 doses ≥5 mg compared with placebo (p < 0.01). Significant (p < 0.001) increases in plasma GLP-1 and PYY levels were seen at these doses, but no clear effect on gastric emptying was demonstrated at the end of treatment. With AZD7687 doses >5 mg/day, gastrointestinal (GI) side effects increased; 11/18 of these participants discontinued treatment owing to diarrhoea. Altered lipid handling and hormone secretion in the gut were demonstrated during 1-week treatment with the DGAT1 inhibitor AZD7687. However, the apparent lack of therapeutic window owing to GI side effects of AZD7687, particularly diarrhoea, makes the utility of DGAT1 inhibition as a novel treatment for diabetes and obesity questionable.

Proof of mechanism for the DGAT1 inhibitor AZD7687: results from a first‐time‐in‐human single‐dose study

Inhibition of diacylglycerol acyltransferase 1 (DGAT1), which catalyses the final step in triacylglycerol (TAG) assembly, is suggested as a treatment for type 2 diabetes and obesity based on animal data indicating insulin sensitization and weight reduction. This first-time-in-human single ascending dose study explored the safety, tolerability, pharmacokinetics and pharmacodynamics of the selective DGAT1 inhibitor AZD7687. Eighty healthy male subjects were enrolled. In each of 10 cohorts, six subjects received the same dose of AZD7687 orally (range across cohorts 1-60 mg) and two placebo. Plasma AZD7687 exposure was measured repeatedly. Postprandial serum TAG excursion was measured during 8 h after a standardized mixed meal with fat energy content of 60% (SMM 60%; five cohorts, 1-20 mg), before (baseline) and after dosing, to assess effects on gut DGAT1 activity. AZD7687 markedly reduced postprandial TAG excursion with a steep concentration-effect relationship. Incremental TAG AUC (area under the serum concentration vs. time curve) following SMM 60% was decreased >75% from baseline at doses ≥5 mg (p < 0.0001 vs. placebo). Serum levels of diacylglycerol, specifically measured with mass spectrometry, did not increase after AZD7687 administration. Nausea, vomiting and diarrhoea were reported with increasing doses and they limited dose escalation. Lowering of SMM fat content to 45 or 30% in five cohorts gradually reduced the frequency of gastrointestinal symptoms at a given dose of AZD7687. The attenuating effect of AZD7687 on postprandial TAG excursion provides proof of mechanism with respect to gut DGAT1 inhibition. However, dose and diet-related gastrointestinal side effects may impact further development of DGAT1 inhibitors.

Dietary Cocoa Butter or Refined Olive Oil Does Not Alter Postprandial hsCRP and IL‐6 Concentrations in Healthy Women

Contrary to other long chain saturated fatty acids (SFA), fats high in stearic acid do not raise plasma cholesterol concentrations, however, a slight elevation in inflammatory markers, plasma fibrinogen and interleukin-6 (IL-6), has been observed in the fasting state. The effect of stearic acid on inflammation in the postprandial state has not yet been reported. We conducted a single blind crossover, randomized, postprandial study to compare the effects of a fat load of cocoa butter high in stearic acid and olive oil in ten healthy women. The test meals contained 1 g of fat per kg body weight (mean 62 g). Blood samples were collected at 0 (fasting), 4 and 6 h. Both diets resulted in a significant increase in serum triacylglycerol (TAG) concentration over time (P = 0.003) and a decrease in serum IL-6 concentration after 4 h followed by an increase to post absorptive values after 6 h (P < 0.001); whereas serum high sensitivity C-reactive protein (hsCRP) concentration was not affected. There was no difference between diets in effects on serum TAG, hsCRP and IL-6 concentrations and no association between postprandial lipemia and inflammatory markers. High intake of dietary fats increase postprandial serum TAG, however, may not affect inflammatory markers postprandially. Thus, fat rich in stearic acid does not seem to increase postprandial inflammation.

Dose-Response ofn-3 Polyunsaturated Fatty Acids on Lipid Profile and Tolerability in Mildly Hypertriglyceridemic Subjects

The n-3 polyunsaturated fatty acids (PUFAs) are known to reduce risk for coronary heart disease partly by altering blood lipids. The purpose of this study was to determine the effect of low doses of n-3 PUFAs on the lipid profile and their tolerability in mildly hypertriglyceridemic subjects. Subjects with a serum triacylglycerol (TG) level between 100 and 300 mg/dL were placed on a corn oil placebo (seven capsules per day; single-blind) for 4 weeks and then randomized to continue seven capsules per day of placebo (n = 49) or one of the following doses of n-3 PUFAs for 20 weeks: 0.5 g (n = 51), 1 g (n = 23), or 2 g (n = 12). During the treatment period, 48-50% of the 1-g and 2-g dose groups reported noticing burping (P < .05), and only about half as many in the 0.5-g group noticed burping. Interestingly, 2% of those assigned to the placebo did report a fishy burping during the study, but this dropped back to nearly 0% by week 20. There was no significant effect for any dosage group on fasting and postprandial serum TG, chylomicron TG, very-low-density lipoprotein-cholesterol, or high-density lipoprotein-cholesterol concentration. However, 1-g and 2-g n-3 PUFA treatments significantly increased total cholesterol and low-density lipoprotein-cholesterol concentration. In addition, all doses of n-3 PUFA treatments significantly increased plasma phospholipid n-3 PUFAs. We conclude that doses of n-3 PUFAs of 0.5-2 g/day in healthy volunteers with above average TG levels did not have beneficial effects on their lipid profiles.

Effect of Diacylglycerol on Postprandial Serum Triacylglycerol Concentration: A Meta‐analysis

Diacylglycerol (DAG) supplementation has been shown to be associated with the reduction of postprandial triacylglycerol (TAG) concentration, although the extent of the association is uncertain. We quantitatively examined the effect of dietary DAG on postprandial serum TAG concentration by conducting a meta-analysis of randomized controlled trials. Potential papers were initially searched for in the electronic databases of Medline, Embase and Cochrane library. Inclusion criteria required the trial to be randomized with DAG as the treatment group, and TAG as the control group. Information was extracted independently by two investigators and the effect of DAG on postprandial TAG concentration was examined in Review Manager 4.2. Seven papers were included in the statistic pooling. DAG supplementation reduced the increment of postprandial TAG concentration significantly at postprandial 2 h (Weighted mean difference (WMD) -0.07 mmol/L; 95% CI -0.13 to 0.00 mmol/L; P = 0.05), 4 h (WMD -0.15 mmol/L; 95% CI -0.24 to -0.06 mmol/L; P = 0.002) and 6 h (WMD -0.14 mmol/L; 95% CI -0.23 to -0.05 mmol/L; P = 0.002). Linear regression showed that the effect of DAG was positively correlated with the daily dosage at 2 h (P = 0.095) and 6 h (P = 0.053) after lipid loading. In conclusion, compared with TAG oil, DAG reduced the postprandial serum TAG concentration at 2 h, 4 h and 6 h postprandial and was positively correlated with daily dosage.

Effects of continuous versus accumulated activity patterns on postprandial triacylglycerol concentrations in obese men

There is limited information regarding the effects of short (<10 min) bouts of activity on postprandial lipaemia and no studies are available regarding the effects of short bouts of activity on postprandial lipaemia in obese men. The objective of this study was to compare the effects of accumulating ten, 3-min bouts of exercise versus one 30 min bout of exercise on postprandial serum triacylglycerol (TAG) concentrations in obese men. Each subject completed three 2-day trials at least 1 week apart in a randomized, repeated-measures design. On day 1, subjects rested (no exercise) or cycled at 60% of maximum heart rate in either ten, 3-min bouts (30 min rest between each), or one continuous 30-min bout. On day 2 of each trial, after an overnight fast, the subjects consumed a standardized test meal for breakfast. Venous blood samples were obtained in the fasted state (0 h), and 2, 4 and 6 h postprandially on day 2. Eight sedentary men (age: 27+/-2 years) with body mass index between 25 and 37 kg/m(2). Postprandial TAG, non-esterified fatty acids, 3-hydroxybutyrate, insulin and glucose were determined. Total area under the postprandial serum TAG concentrations versus time curve was 18% (P=0.042) and 15% (P=0.032) lower throughout day 2 of both the accumulated exercise trial and the continuous exercise trial, respectively, compared with the control trial with little difference between exercise trials. At 30 min of moderate cycling (0.87 MJ per 30 min) accumulated in short bouts is equally effective in reducing postprandial serum TAG concentrations as one continuous 30 min bout of cycling in obese men.

Subchronic 4-month oral toxicity study of dried Smallanthus sonchifolius (yacon) roots as a diet supplement in rats

Yacon roots are a rich source of fructooligosaccharides (FOS) and have a long use tradition as food in the Andean region. However, there are no published reports regarding their toxicology and use safety. The aim of this study was to analyze the effects of subchronic (4-months) oral consumption of dried yacon root flour as a diet supplement using normal Wistar rats. Two daily intake levels were used, equivalent to 340 mg and 6800 mg FOS/body weight, respectively. Yacon administered as a diet supplement was well tolerated and did not produce any negative response, toxicity or adverse nutritional effect at both intake levels used. Yacon root consumption showed no hypoglycemic activity in normal rats and resulted in significantly reduced post-prandial serum triacylglycerol levels in both doses assayed. Conversely, serum cholesterol reduction was not statistically significant. Cecal hypertrophy was observed in rats fed only the high dose. Our results indicating lack of toxicity and a certain beneficial metabolic activity in normal rats warrant further experiments with normal subjects and patients suffering metabolic disorders. They should also be considered when establishing the regulatory framework of this natural product by national health authorities and international trade agencies.

Effects of diacylglycerol ingestion on postprandial hyperlipidemia in diabetes

Background We previously reported that diacylglycerol (DAG) as compared with triacylglycerol (TAG) suppressed increases in postprandial lipids in healthy volunteers. This study was to investigate the effects of DAG on postprandial lipids, particularly remnant lipoproteins in diabetics. Methods Emulsified DAG oil or TAG oil with a fatty acid composition similar to DAG oil was orally administered (30 g fat/m 2 of body surface) to moderately controlled six diabetics, with hemoglobin A1c (HbA1c) below 8%, after fasting for at least 12 h in a randomized crossover manner. Serum cholesterol and TAG, lipids in remnant-like particles (RLP), and other lipid parameters including serum ketone bodies were measured prior to and 2, 4, and 6 h after fat loading. Results DAG loading significantly suppressed increases in postprandial serum TAG and lipids in RLP as compared with TAG loading. The incremental area under the curve (IAUC) for serum TAG and that for lipids in RLP with DAG loading were also significantly smaller than those with TAG loading. However, changes in serum levels of insulin, free fatty acids, and ketone bodies during fat loading were essentially the same for DAG and TAG. Conclusions This pilot study suggests that substituting DAG intake for TAG may be beneficial to moderately controlled diabetics due to its effect in reducing postprandial hyperlipidemia.

Effects of diacylglycerol administration on serum triacylglycerol in a patient homozygous for complete lipoprotein lipase deletion

We investigated postprandial and long-term effects of dietary diacylglycerol (DAG) on serum triacylglycerol (TAG) levels in a 34-year-old man homozygous for complete lipoprotein lipase deletion (LPL deletion). In study 1, Three different oils (DAG, TAG, or medium-chain fatty acid TAG [MCT]) were ingested to examine differences in the postprandial serum TAG response. Postprandial serum TAG levels after DAG oil ingestion were lower than those after TAG oil ingestion and similar to those after MCT oil ingestion. In study 2, the patient was allowed to ingest ordinary cooking oil for 2 months and then DAG oil (containing 80% DAG; target, 20 g/d) for the next 3 months. During the test period, serum TAG levels were measured and dietary evaluations were performed every month. The patient was provided with dietary instruction and consultation at each clinical visit. Serum TAG levels were 1939 to 2525 mg/dL when he used ordinary cooking oil, 1926 to 1173 mg/dL when he used ordinary cooking oil together with DAG oil, and 749 mg/dL when he used DAG oil alone. The TAG intake decreased from 86.9 to 43.0 g and the DAG intake increased from 0.9 to 12.4 g during the study period. Subsequently, 45 g DAG oil (equivalent to 36 g DAG) per day was consumed, and the serum TAG level increased to 2195 mg/dL. Although there was a positive correlation between the TAG intake and serum TAG levels during the period of DAG oil use ( P < .01, y = 33.7 x − 583.1), there was no such correlation between DAG oil intake and serum TAG levels. These results suggested that substitution of 12.0 g/d DAG (equivalent to 15 g DAG oil) for TAG oil had the same effect as reducing TAG oil consumption for controlling the serum TAG levels in an LPL-depleted patient with hypertriglyceridemia. In conclusion, the results of study 1 and study 2 demonstrate that DAG oil might be replaced by MCT oil as cooking oil for those with LPL deletion.