Postprandial Triacylglycerol Research Articles

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.

The leptin receptor Gln223Arg polymorphism (rs1137101) mediates the postprandial lipaemic response, but only in males

ObjectiveAn exaggerated postprandial triacylglycerol (TAG) response is an important determinant of cardiovascular disease risk. With increased recognition of the role of leptin in systemic macronutrient metabolism, we used a candidate gene approach to examine the impact of the common leptin receptor (LEPR) Gln223Arg polymorphism (rs1137101) on postprandial lipaemia. Methods and resultsHealthy adults (n = 251) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (t = 0) and lunch (t = 330 min). Fasting total- and low-density lipoprotein cholesterol were 9% lower in the ArgArg than GlnArg group (P < 0.04), whereas fasting TAG was 27% lower in the ArgArg than GlnGln group (P < 0.02). The magnitude of the postprandial TAG response was also significantly lower in the ArgArg compared with the GlnArg and GlnGln genotypes, with a 26% lower area under the curve (AUC) and incremental AUC in the ArgArg individuals (P ≤ 0.023). Genotype*gender interactions were evident for fasting and postprandial TAG responses (P < 0.05), with the genotype effect only evident in males. Regression analysis indicated that the LEPR genotype and genotype*gender interactions were independent predictors of the TAG AUC, accounting for 6.3% of the variance. Our main findings were replicated in the independent LIPGENE-Cordoba postprandial cohort of metabolic syndrome subjects (n = 75), with a 52% lower TAG AUC in the ArgArg than GlnGln male subjects (P = 0.018). ConclusionWe report for the first time that the common LEPR Gln223Arg genotype is an important predictor of postprandial TAG in males. The mechanistic basis of these associations remains to be determined.

Increased plasma availability of l-arginine in the postprandial period decreases the postprandial lipemia in older adults

ObjectiveOlder adults have exaggerated postprandial lipemia, which increases their risk for cardiovascular disease. We sought to determine the effects of increased plasma l-arginine (L-ARG) availability on the oxidation of ingested fat (enriched with [1,1,1-13C]-triolein) and plasma triacylglycerol (TG) concentrations during the postprandial period in older subjects. MethodsOn one day, eight healthy subjects (67.8 ± 1.3 y old) received an intravenous infusion of L-ARG during the first hour of the postprandial period (L-ARG trial), while on a separate day, and in a randomized order, they received saline (control trial). ResultsThe 8-h area under the plasma concentration–time curve describing the postprandial plasma TG concentrations was considerably lower in the L-ARG trial than in the control trial (−4 ± 21 versus 104 ± 21 mg ∙ dL−1 ∙ h−1, P < 0.01). The rate of the postprandial oxidation of the ingested lipid was not different between the trials, but the average contribution of the ingested oleate to the oleate of the TG of the plasma small TG-rich lipoproteins (Svedberg flotation index 20–400) was lower in the L-ARG trial (11 ± 1 versus 18 ± 2%, P < 0.01). L-ARG infusion also decreased the 8-h area under the plasma concentration–time curve of the plasma free fatty acid concentrations derived from the ingested fat compared with the saline infusion (0.77 ± 0.09 versus 1.11 ± 0.08; mmol ∙ L−1 ∙ h−1, P < 0.01). ConclusionIncreasing the plasma L-ARG availability during the postprandial period decreases the postprandial lipemia in older adults, in association with a decrease in the postprandial contribution of ingested lipids into TGs of the plasma small TG-rich lipoproteins.

Meal Frequency Differentially Alters Postprandial Triacylglycerol and Insulin Concentrations in Obese Women

Meal Frequency Differentially Alters Postprandial Triacylglycerol and Insulin Concentrations in Obese Women

Triacylglycerol-rich lipoproteins protect lipoprotein lipase from inactivation by ANGPTL3 and ANGPTL4

Lipoprotein lipase (LPL) is important for clearance of triacylglycerols (TG) from plasma both as an enzyme and as a bridging factor between lipoproteins and receptors for endocytosis. The amount of LPL at the luminal side of the capillary endothelium determines to what extent lipids are taken up. Mechanisms to control both the activity of LPL and its transport to the endothelial sites are regulated, but poorly understood. Angiopoietin-like proteins (ANGPTLs) 3 and 4 are potential control proteins for LPL, but plasma concentrations of ANGPTLs do not correlate with plasma TG levels. We investigated the effects of recombinant human N-terminal (NT) ANGPTLs3 and 4 on LPL-mediated bridging of TG-rich lipoproteins to primary mouse hepatocytes and found that the NT-ANGPTLs, in concentrations sufficient to cause inactivation of LPL in vitro, were unable to prevent LPL-mediated lipoprotein uptake. We therefore investigated the effects of lipoproteins (chylomicrons, VLDL and LDL) on the inactivation of LPL in vitro by NT-ANGPTLs3 and 4 and found that LPL activity was protected by TG-rich lipoproteins. In vivo, postprandial TG protected LPL from inactivation by recombinant NT-ANGPTL4 injected to mice. We conclude that lipoprotein-bound LPL is stabilized against inactivation by ANGPTLs. The levels of ANGPTLs found in blood may not be sufficient to overcome this stabilization. Therefore it is likely that the prime site of action of ANGPTLs on LPL is in subendothelial compartments where TG-rich lipoprotein concentration is lower than in blood. This could explain why the plasma levels of TG and ANGPTLs do not correlate.

High-intensity exercise attenuates postprandial lipaemia and markers of oxidative stress

Regular exercise can reduce the risk of CVD (cardiovascular disease). Although moderate-intensity exercise can attenuate postprandial TAG (triacylglycerol), high-intensity intermittent exercise might be a more effective method to improve health. We compared the effects of high-intensity intermittent exercise and 30min of brisk walking on postprandial TAG, soluble adhesion molecules and markers of oxidative stress. Nine men each completed three 2-day trials. On day 1, subjects rested (control), walked briskly for 30min (walking) or performed 5×30s maximal sprints (high-intensity). On day 2, subjects consumed a high-fat meal for breakfast and 3h later for lunch. Blood samples were taken at various times and analysed for TAG, glucose, insulin, ICAM-1 (intracellular adhesion molecule-1), VCAM-1 (vascular adhesion molecule-1), TBARS (thiobarbituric acid- reactive substances), protein carbonyls and β-hydroxybutyrate. On day 2 of the high-intensity trial, there was a lower (P<0.05) incremental TAG AUC (area under the curve; 6.42±2.24mmol/l per 7h) compared with the control trial (9.68±4.77mmol/l per 7h) with no differences during day 2 of the walking trial (8.98±2.84mmol/l per 7h). A trend (P=0.056) for a reduced total TAG AUC was also seen during the high-intensity trial (14.13±2.83mmol/l per 7h) compared with control (17.18±3.92mmol/l per 7h), walking showed no difference (16.33±3.51mmol/l per 7h). On day 2 of the high-intensity trial plasma TBARS and protein carbonyls were also reduced (P<0.05) when compared with the control and walking trials. In conclusion, high-intensity intermittent exercise attenuates postprandial TAG and markers of oxidative stress after the consumption of a high-fat meal.

The effect of FABP2 promoter haplotype on response to a diet with medium-chain triacylglycerols

The fatty-acid-binding protein-2 (FABP2) gene has been proposed as a candidate gene for diabetes because the encoded protein is involved in fatty acid absorption and therefore may affect insulin sensitivity and glucose metabolism. The rare haplotype (B) of its promoter was shown to be associated with a lower risk for type 2 diabetes. The aim of this study was to investigate whether a polymorphism in the FABP2 promoter does affect the metabolic response to either an medium-chain triacylglycerol (MCT) or an long-chain triacylglycerol (LCT) diet, which were suggested to differ in transport mechanisms, in affinity to FABP2, in activating transcription factors binding to the FABP2 promoter and in their effects on insulin sensitivity. We studied 82 healthy male subjects varying in the FABP2 promoter (42 homozygous for common haplotype (A), 40 homozygous for the rare haplotype (B)) in an interventional study with either an MCT or LCT diet over 2weeks to examine gene-nutrient interaction. The saturation grade of MCT was adjusted to that of the LCT fat. We determined glucose, insulin, triacylglycerols (TGs), chylomicron triacylglycerols and cholesterol before and after a standardised mixed meal before and after the intervention. HDL cholesterol increased in all groups, which was most pronounced in subjects homozygous for the common promoter haplotype A who received MCT diet (P=0.001), but not significant in homozygous rare haplotype B subjects who received MCT fat. Subjects homozygous for FABP2 haplotype A showed a significant decrease in fasting and postprandial glucose (P=0.01, 0.04, respectively) and a decrease in insulin resistance (HOMA-IR, P=0.04) during LCT diet. After correction for multiple testing, those effects did not remain significant. Fasting and postprandial triacylglycerols, LDL cholesterol, chylomicron TGs and cholesterol were not affected by genotype or diet. MCT diet increased HDL cholesterol dependent on the FABP2 promoter haplotype. The effects of the promoter haplotype B could be mediated by PPARγ, which is upregulated by medium-chain fatty acids.

Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study

Pharmacological augmentation of glucagon-like peptide 1 receptor signalling by dipeptidyl peptidase 4 (DPP-4) inhibition reduced intestinal lipoprotein secretion in experimental studies, suggesting that DPP-4 inhibitors may ameliorate dyslipidaemia and thus reduce cardiovascular risk in patients with type 2 diabetes. We assessed the effects of alogliptin (Alo) and Alo co-administered with pioglitazone (Pio) vs placebo (Pbo) on triacylglycerol (TG)-rich lipoproteins in type 2 diabetes before and following a high-fat meal. Seventy-one patients (age 18-70 years), who did not reach HbA(1c) 6.5% (48 mmol/mol) with lifestyle and/or metformin, sulfonylurea or glinide therapy, participated in this 16 week, double-centre (university hospitals) Pbo-controlled parallel-group study. All participants, people doing measurements or examinations, and people assessing the outcomes were blinded to group assignment. Fasting TG 1.7-5.0 mmol/l was among the entry criteria. Patients received a high-fat mixed meal before and 4 and 16 weeks after randomisation (allocation by central office) to Alo (n = 25), Alo/Pio (n = 22) or Pbo (n = 24). Blood was sampled at pre-specified intervals, starting at 15 min before and ending 8 h after meal ingestion. At week 16, Alo (n = 25) and Alo/Pio (n = 21) vs Pbo (n = 24) produced similar significant reductions in total postprandial TG response (incremental AUC [iAUC]; p < 0.001), as well as in chylomicron TG (p < 0.001) and VLDL1 TG iAUCs (p < 0.001 and p = 0.012, respectively). Postprandial chylomicron apolipoprotein B-48 iAUC showed a significant decrease after Alo treatment (p = 0.028), and a non-significant trend towards a decrease with Alo/Pio (p = 0.213). The incidence of adverse events was low and consistent with previous studies. Treatment with Alo and Alo/Pio produced significant reductions in postprandial TG and TG-rich lipoproteins, contributing to an improved overall cardiometabolic risk profile in type 2 diabetes. The data support the concept that incretins not only modulate glucose metabolism but also influence chylomicron metabolism in intestinal cells. ClinicalTrials.gov number NCT00655863.

Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms

Background and aimsThe polyphenol quercetin may prevent cardiovascular diseases due to its vasorelaxant and anti-oxidative properties. We investigated the effects of quercetin on risk factors of atherosclerosis, biomarkers of inflammation and oxidative stress, depending on the apolipoprotein E (APOE) genotype. Methods and resultsIn a double-blind crossover study 49 healthy male subjects with APOE genotype 3/3 (n = 19), 3/4 (n = 22) and 4/4 (n = 8) consumed 150 mg/d quercetin or placebo for 8 weeks each, intermitted by a three-week washout phase. After each intervention, endothelial function, anthropometry, metabolic and inflammatory parameters were measured in the fasting and postprandial state following a standardized lipid-rich meal.Endothelial function was not changed. In all subjects combined, quercetin significantly decreased waist circumference (P = 0.004) and postprandial systolic blood pressure (P = 0.044). Postprandial triacylglycerol concentrations were significantly decreased and HDL-cholesterol concentrations increased after quercetin as compared to placebo consumption (P = 0.025). Quercetin also moderately increased levels of TNFα (P = 0.024). There was a significant gene–diet interaction for waist circumference and for body mass index (BMI). ConclusionsQuercetin supplementation improved some risk factors of cardiovascular disease, yet exerted slightly pro-inflammatory effects. Genotype-dependent effects were seen only on waist circumference and BMI.

A sequential two meal challenge reveals abnormalities in postprandial TAG but not glucose in men with increasing numbers of metabolic syndrome components

ObjectiveTo examine the impact of increasing numbers of metabolic syndrome (MetS) components on postprandial lipaemia. MethodsHealthy men (n=112) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (0min) and lunch (330min). Lipids, glucose and insulin were measured in the fasting sample, with triacylglycerol (TAG), non-esterified fatty acids and glucose analysed in the postprandial samples. ResultsSubjects were grouped according to the number of MetS components regardless of the combinations of components (0/1, 2, 3 and 4/5). As expected, there was a trend for an increase in body mass index, blood pressure, fasting TAG, glucose and insulin, and a decrease in fasting high-density lipoprotein cholesterol with increasing numbers of MetS components (P≤0.0004). A similar trend was observed for the summary measures of the postprandial TAG and glucose responses. For TAG, the area under the curve (AUC) and maximum concentration (maxC) were significantly greater in men with ≥3 than <3 components (P<0.001), whereas incremental AUC was greater in those with 3 than 0/1 and 2, and 4/5 compared with 2 components (P<0.04). For glucose, maxC after the test breakfast (0–330min) and total AUC (0–480min) were higher in men with ≥3 than <3 components (P≤0.001). ConclusionsOur data analysis has revealed a linear trend between increasing numbers of MetS components and magnitude (AUC) of the postprandial TAG and glucose responses. Furthermore, the two meal challenge discriminated a worsening of postprandial lipaemic control in subjects with ≥3 MetS components.

Physical Activity Status and Postprandial Lipaemia in Older Adults

Physical activity-induced lowering of postprandial lipaemia is short-lived. However, little is known regarding the role of physical activity status on postprandial lipaemia. The purpose of the present study was to compare postprandial triacylglycerol concentrations in active and inactive older adults. A total of 26 older adults (aged 69.8±0.9 years, mean±SEM; 10 male and 16 female) were analysed in a cross-sectional design. Based on accelerometer data, participants were divided into either the active group (≥150 min/week of moderate-intensity physical activity, N=15) or the inactive group (<150 min/week of moderate-intensity physical activity, N=11). After a 48-h period of physical activity avoidance and a 10-h overnight fast, participants consumed a test meal of moderate fat content (35%). Capillary blood samples were collected in the fasted state and at 2, 4, and 6 h postprandially. After adjusting for fasting triacylglycerol concentrations, body mass, body mass index and waist circumference, postprandial capillary triacylglycerol concentrations were significantly lower in the active than inactive group ( P=0.046). These findings demonstrate that regular physical activity lowers postprandial lipaemia independent of the acute effects of physical activity in older adults.

A sodium-bicarbonated mineral water reduces gallbladder emptying and postprandial lipaemia: A randomised four-way crossover study

Sodium-bicarbonated mineral waters are reported to have beneficial digestive and hypocholesterolaemic properties. The aim of the study was to investigate the effects of consumption of a sodium-bicarbonated mineral water (BW) with or without a meal, compared to a low mineral content water as the control water (CW), on postprandial serum triacylglycerols (TAG), cholecystokinin (CCK) and gallbladder volume. The study design was a four-way randomised controlled crossover trial. Healthy adult men and women (>18 and <40 years, TAG <2.82 mmol/L) consumed 0.5 L of CW + standard meal; 0.5 L of BW + standard meal; and 0.5 L of CW without meal or 0.5 L of BW without meal. BW consumed without meal had no significant effect on the study parameters compared to CW. However, BW with meal induced a lower concentration of serum TAG at 30 min (p = 0.01) and 60 min (p = 0.03) postprandial times, lower CCK concentrations at 30 min (p = 0.002), and higher gallbladder volume at 30 min (p = 0.03), 60 min (p = 0.01) and 120 min (p = 0.04). Gallbladder ejection fraction was lower with the BW (p = 0.03), whilst area under the curve and peak contraction amplitude (lowest gallbladder volume) were higher (p = 0.01, p = 0.02, respectively) compared to the CW. Consumption of BW with a meal induces lower levels of CCK and reduces gallbladder emptying and postprandial TAG levels. It is proposed that this sodium-bicarbonated mineral water could be used as part of the habitual diet by the general population in order to reduce cardiovascular risk.

Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast

BackgroundCinnamon has been shown to delay gastric emptying of a high-carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it is dietary fat which is implicated in the etiology and is associated with obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and glycemic responses, oxidative stress, arterial stiffness, as well as appetite sensations and subsequent food intake following a high-fat meal.MethodsA single-blind randomized crossover study assessed nine healthy, young subjects. GE rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined using the 13C octanoic acid breath test. Breath, blood samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty acid intake relationships were also examined.ResultsCinnamon did not change gastric emptying parameters, postprandial triacylglycerol or glucose concentrations, oxidative stress, arterial function or appetite (p < 0.05). Strong relationships were evident (p < 0.05) between GE Thalf and 1-day palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3 intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial stiffness and oxidative stress following a HF meal.Conclusions3 g cinnamon did not alter the postprandial response to a high-fat test meal. We find no evidence to support the use of 3 g cinnamon supplementation for the prevention or treatment of metabolic disease. Dietary fatty acid intake requires consideration in future gastrointestinal studies.Trial registrationTrial registration number: at http://www.clinicaltrial.gov: NCT01350284

Impaired insulin sensitivity is accompanied by disturbances in skeletal muscle fatty acid handling in subjects with impaired glucose metabolism

To determine insulin sensitivity and skeletal muscle fatty acid (FA) handling at baseline and after a high-fat mixed meal in impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and normal glucose tolerance (NGT) subjects. In this multi-center study, insulin sensitivity and β-cell function were assessed (n=102), using a euglycemic-hyperinsulinemic and hyperglycemic clamp with additional arginine stimulation and a 75 g oral glucose tolerance test. Fasting and postprandial skeletal muscle FA handling was examined in a substudy using the forearm balance technique (n=35). A total of 102 subjects with IFG (n=48), IGT (n=12), IFG/IGT (n=26) and NGT (n=16). IFG, IGT and IFG/IGT subjects had lower insulin sensitivity with no differences between groups, and lower impaired β-cell function compared with NGT controls. The early postprandial increase in triacylglycerol (TAG) concentration was higher (iAUC(0-2 h) IFG: 238.4±26.5, IGT: 234.0±41.0 and NGT: 82.6±13.8 μmol l(-1) min(-1), both P<0.05) and early TAG extraction was increased (AUC(0-2 h) IFG: 56.8±9.0, IGT: 52.2±12.0 and NGT: 3.8±15.4 nmol·100 ml(-1) min(-1), P<0.05 and P=0.057, respectively) in both IFG and IGT subjects. IFG, IGT and IFG/IGT subjects have lower insulin sensitivity and impaired β-cell function compared with age- and BMI-matched NGT controls. The increased postprandial TAG response and higher muscle TAG extraction in both IFG and IGT compared with NGT may lead to ectopic fat accumulation in the skeletal muscle, thereby contributing to insulin resistance.

Validity of abbreviated oral fat tolerance tests for assessing postprandial lipemia

Postprandial lipemia is assessed using the oral fat tolerance test (OFTT), a six-hour procedure requiring hourly blood sampling. In order to simplify the test, we investigated whether a)asingle postprandial triacylglycerol concentration, b) an OFTT lasting less than six hours or c) an OFTT requiring fewer blood samples, may accurately assess postprandial lipemia under various conditions. Seventy-two subjects underwent a conventional OFTT. Predictability of single-point concentrations and time-shortened tests was assessed using linear regression and re-sampling analysis. Validity of reduced-sampling tests was assessed using Pearson's correlation coefficients and Bland-Altman analysis. a) A single-point triacylglycerol concentration (3 or 4h postprandially) did not present significant correlation with postprandial lipemia in the hypetriacylglycerolemic, exercise and energy restriction groups (P>0.05), b) Time-shortened OFTT (4h) was able to predict postprandial lipemia in every group studied (R(2)=0.707-0.970, P<0.01), except the hypertriacylglycerolemics (P=0.338), c) Reduced-sampling OFTT (3 or 4 samples) was able to assess postprandial lipemia in every group as well as in the overall sample (r=0.874-0.997, P<0.05). A more convenient, reduced-sampling OFTT may be used alternatively to the conventional OFTT, whereas a time-shortened OFTT may be appropriate only for healthy people.

Identification of Diacylglycerol Acyltransferase Inhibitors from Rosa centifolia Petals

Diacylglycerol acyltransferase (DGAT) catalyzes the final step of triacylglycerol (TAG) synthesis, and is considered as a potential target to control hypertriglyceridemia or other metabolic disorders. In this study, we found that the extract of rose petals suppressed TAG synthesis in cultured cells, and that the extract showed DGAT inhibitory action in a dose-dependent manner. Fractionation of the rose extract revealed that the DGAT inhibitory substances in the extract were ellagitannins; among them rugosin B, and D, and eusupinin A inhibited DGAT activity by 96, 82, and 84% respectively, at 10μM. These substances did not inhibit the activities of other hepatic microsomal enzymes, glucose-6-phosphatase and HMG-CoA reductase, or pancreatic lipase, suggesting that ellagitannins inhibit DGAT preferentially. In an oral fat load test using mice, postprandial plasma TAG increase was suppressed by rose extract; TAG levels 2h after the fat load were significantly lower in mice administered a fat emulsion containing rose extract than in control mice (446.3±33.1 vs 345.3±25.0mg/dL, control vs rose extract group; P<0.05). These results suggest that rose ellagitannins or rose extract could be beneficial in controlling lipid metabolism and used to improve metabolic disorders.

Lifestyle Intervention Leading to Moderate Weight Loss Normalizes Postprandial Triacylglycerolemia Despite Persisting Obesity

Obesity is associated with impaired postprandial triacylglycerolemia, an independent risk factor for cardiovascular disease. Given that obesity is hard to treat, efforts should focus on treating its comorbidities. We aimed to investigate whether moderate weight loss normalizes postprandial triacylglycerol (TAG) concentrations, in the absence of the acute effects of negative energy balance. For this purpose, postprandial lipemia was investigated in eight obese but otherwise healthy, sedentary men (age: 41.3 ± 4.1 years, BMI: 36.5 ± 1.6 kg·m(-2)), once before and again after a 10% weight loss followed by ≥4 weeks of weight maintenance, and was compared with that of eight age-matched healthy lean men (BMI: 24.7 ± 0.6 kg·m(-2)). Dietary intervention consisted of reduced carbohydrate and saturated fat intake and increased monounsaturated fat intake. Obese volunteers were advised to increase physical activity using pedometers to record daily activity. Postprandial triacylglycerolemia after weight loss was reduced by 27-46% (P < 0.05), and became similar to that of lean men despite persisting obesity (BMI after weight loss: 32.9 ± 1.5 kg·m(-2)). Reduction in postprandial TAG responses was inversely correlated with the decrease in postprandial insulin sensitivity index (ISI) after weight loss (r = -0.714, P = 0.047). We conclude that moderate weight loss induced by a low-carbohydrate and saturated fat diet and a slight increase in daily physical activity normalizes postprandial triacylglycerolemia in obese men, independently of acute diet-induced negative energy balance, and possibly through enhancement of insulin action.

Effect of energy expenditure on postprandial triacylglycerol in adolescent boys

This study examined the effects of 30 and 60 min of moderate intensity exercise on postprandial triacylglycerol concentration [TAG] in 11 healthy, 13-year-old boys. The boys completed three counterbalanced conditions. On day 1, they either rested (CON), or jogged for 30 min (EX30) or 60 min (EX60) at 55% peak [Formula: see text] Following a 12-h fast, on day 2 a capillary blood sample was taken for fasting [TAG] before a high fat milkshake was consumed. Further blood samples were taken every hour over a 6-h postprandial rest period for [TAG]. The estimated energy expenditure for EX30 (982 kJ) was doubled in EX60 (1967 kJ). Differences in fasting [TAG] between the conditions were small (ES = 0.23, P = 0.35). Differences in postprandial TAG over time between conditions were identified (ES = 0.41, P = 0.03). Mean [TAG] was lower in EX60 than CON (-33 to -3%, P = 0.03) with a similar strong trend for EX30 (-29 to 1%, P = 0.06); EX60 and EX30 were not different from each other (-21 to 14%, P = 0.62). The total area under the [TAG] versus time curve was different between conditions (ES = 0.42, P = 0.03). Again, EX60 was lower than CON (-31 to -2%, P = 0.02) with a strong trend for EX30 (-31 to 4%, P = 0.06); EX30 and EX60 were not different from each other (-17 to 16%, P = 0.58). This study shows for the first time that both 30 and 60 min of jogging, with energy expenditures equivalent to 982 and 1,967 kJ, attenuates postprandial [TAG] in adolescent boys, but not in a dose-dependent manner.

Is the beneficial effect of prior exercise on postprandial lipaemia partly due to redistribution of blood flow?

Preprandial aerobic exercise lowers postprandial lipaemia (a risk factor for coronary heart disease); however, the mechanisms responsible are still not clear. The present study investigated whether blood flow to skeletal muscle and/or the liver was increased in the postprandial period after exercise, relative to a control trial, and whether this resulted from increased cardiac output or redistribution of flow. Eight overweight inactive males, aged 49.4±10.5years (mean±S.D.), acted as their own controls in a counterbalanced design, either walking briskly for 90min at 60% V̇O2max (maximal oxygen uptake), or resting in the lab, on the evening of day 1. The following morning, a fasting blood sample was collected, participants consumed a high-fat breakfast, and further venous blood samples were drawn hourly for 6h. Immediately after blood sampling, Doppler ultrasound was used to measure cardiac output and blood flow through both the femoral artery of one leg and the hepatic portal vein, with the ultrasonographer blinded to trial order. The total postprandial triacylglycerol response was 22% lower after exercise (P=0.001). Blood flow through the femoral artery and the hepatic portal vein was increased by 19% (P<0.001) and 16% (P=0.033), respectively, during the 6-h postprandial period following exercise; however, postprandial cardiac output did not differ between trials (P=0.065). Redistribution of blood flow, to both exercised skeletal muscle and the liver, may therefore play a role in reducing the plasma triacylglycerol response to a high-fat meal on the day after an exercise bout.

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.