High-fat Meal Challenge Research Articles

Postprandial Skeletal Muscle Metabolism Following a High Fat Diet in Sedentary and Endurance Trained Males

ObjectiveFasting and postprandial metabolism are adversely affected by a sedentary lifestyle. However, the role of the prevailing diet remains unclear. The objective of the present study was to determine the influence of a high fat diet (HFD) on fasting and postprandial skeletal muscle substrate metabolism in sedentary compared with endurance trained (ET) humans.MethodsMetabolically healthy sedentary (n=17) and ET (n=7) males were control‐fed a 10‐day isocaloric moderate fat diet (30% fat [<10% saturated fat], 55% carbohydrate) followed by a 5‐day isocaloric HFD (55% fat [25% saturated fat], 30% carbohydrate). Before and after the HFD participants completed a high fat meal challenge (820 kcals; 63% fat [26% saturated fat], 25% carbohydrate) in which skeletal muscle biopsies were taken in the fasted and 4‐hour fed states. Complete fat, glucose, and pyruvate oxidation were assessed by measuring 14CO2 production in homogenized skeletal muscle incubated with radio‐labeled substrates. Incomplete fat oxidation was assessed by measuring 14C‐labeled acid soluble metabolites. Total fat oxidation was comprised of the sum of complete and incomplete fat oxidation. A substrate preference assay was performed by assessing the free fatty acid (FFA)‐induced suppression of [1‐14C]‐pyruvate oxidation. The meal effect for each substrate oxidation measure was calculated as the percent change from the fasted to 4‐hour fed state.ResultsThe meal effect for glucose oxidation was not altered by the HFD in the ET group (128 ± 92% vs. 41 ± 15%, P=0.375) but was reduced in the sedentary group (78 ± 26% vs. −21 ± 6%, P=0.002). The meal effect for pyruvate oxidation was similar between ET and sedentary groups before the HFD (34 ± 13% vs. 14 ± 17%, respectively; P=0.145) but was lower in the sedentary compared with the ET group after the HFD (−16 ± 6% vs. 24 ± 17%, P=0.047). The meal effect for substrate preference as indicated by FFA‐induced suppression of pyruvate oxidation was retained after the HFD in the ET group (20 ± 4% vs. 41 ± 21%, P=0.342) but was reduced in the sedentary group (34 ± 7% vs. 4 ± 5%, P=0.003). The meal effects for incomplete and total fat oxidation tended to decrease as a result of the HFD in the overall sample (P=0.075 and P=0.062, respectively). There were no physical activity group or HFD effects on meal effects for complete fat oxidation or the ratio of complete‐to‐incomplete fat oxidation.ConclusionsThese findings suggest skeletal muscle from sedentary individuals displays reduced postprandial glucose oxidation, yet pyruvate is preferred over fatty acids as an oxidative substrate following consumption of a HFD. These data highlight the need to better understand key regulatory nodes in skeletal muscle substrate metabolism between ET and sedentary humans.Support or Funding InformationADA‐07‐12 (MWH); Virginia Tech Translational Obesity Research IGEPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

High‐Protein Diet‐Induced Changes in Body Composition and Metabolic Flexibility in Women: Feasibility of a Novel Template‐based Intervention Delivery Method

Current recommended dietary allowance for protein is 0.8 g/kg/d. Recently, research has posited that this value is insufficient for resistance‐trained individuals and inadequate for the retention of lean mass while on a fat loss diet. Studies support an intake of nearly double the RDA, i.e. ~1.4–2.0 g/kg/day, but effective implementation strategies for achieving this higher protein intake have not been identified. Additionally, metabolic flexibility is the ability to adjust substrate oxidation according to nutrient availability and may be reflective of metabolic health. Whether a higher protein, caloric deficit diet improves metabolic flexibility in resistance‐trained women is not known.PURPOSETo determine the effects of a novel high protein diet template on body composition and metabolic flexibility during an 8‐wk intervention in recreationally resistance trained females.METHODSRecreationally resistance‐trained females (n=7, Age=21.7±2.1 yrs) were underwent baseline and post 8‐wk intervention dual‐energy X‐ray absorptiometry scans, anthropometrics and an acute high fat meal challenge. Baseline (T1) fasting glucose, resting energy expenditure (REE), and lipid (LO) and carbohydrate oxidation (CO) were measured. Participants then consumed a high fat meal (1127±132 kcal; 77±9 g fat) and glucose, REE, LO and CO measurements were taken at 60 (T2), 120 (T3) and 180 (T4) minutes postprandial. The meals contained 61% fat/29% carbohydrate/10% protein and were standardized to participants' body surface area (BSA). Participants were instructed how to follow a high‐protein dietary template (1.5–1.6 g/kg/day) and asked to maintain their resistance training volume and intensity throughout the study. The template was a PDF document containing specific instructions on amounts of lean proteins, vegetables, carbohydrates, and fats to be consumed at each meal throughout the day.RESULTSSignificant decreases were observed in % body fat (pre: 30.7±3.9%, post: 28.3±3.0%; p=0.010), waist circumference (pre: 77.0±4.7 cm, post: 74.4±5.2 cm; p=0.030), and waist‐to‐hip ratio (pre: 0.77±0.04, post: 0.76±0.04; p=0.050), with total body weight (pre: 67.5±6.7 kg, post: 65.5±5.3 kg; p = 0.076) and fat mass (pre: 19.7±3.7 kg, post: 18.6±3.0 kg; p=0.062) approaching significance. There were no significant changes in bone density, lean mass, fasting glucose, REE, LO, or CO.CONCLUSIONSA high protein diet leads to favorable improvements in fat mass, while preserving both lean mass and bone density in resistance trained females, without affecting metabolic flexibility. Our study also supports the feasibility of delivering a dietary intervention in a user‐friendly diet template format.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Metabolic and inflammatory biomarkers are associated with epigenetic aging acceleration estimates in the GOLDN study

BackgroundRecently, epigenetic age acceleration—or older epigenetic age in comparison to chronological age—has been robustly associated with mortality and various morbidities. However, accelerated epigenetic aging has not been widely investigated in relation to inflammatory or metabolic markers, including postprandial lipids.MethodsWe estimated measures of epigenetic age acceleration in 830 Caucasian participants from the Genetics Of Lipid Lowering Drugs and diet Network (GOLDN) considering two epigenetic age calculations based on differing sets of 5′-Cytosine-phosphate-guanine-3′ genomic site, derived from the Horvath and Hannum DNA methylation age calculators, respectively. GOLDN participants underwent a standardized high-fat meal challenge after fasting for at least 8 h followed by timed blood draws, the last being 6 h postmeal. We used adjusted linear mixed models to examine the association of the epigenetic age acceleration estimate with fasting and postprandial (0- and 6-h time points) low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels as well as five fasting inflammatory markers plus adiponectin.ResultsBoth DNA methylation age estimates were highly correlated with chronological age (r > 0.90). We found that the Horvath and Hannum measures of epigenetic age acceleration were moderately correlated (r = 0.50). The regression models revealed that the Horvath age acceleration measure exhibited marginal associations with increased postprandial HDL (p = 0.05), increased postprandial total cholesterol (p = 0.06), and decreased soluble interleukin 2 receptor subunit alpha (IL2sRα, p = 0.02). The Hannum measure of epigenetic age acceleration was inversely associated with fasting HDL (p = 0.02) and positively associated with postprandial TG (p = 0.02), interleukin-6 (IL6, p = 0.007), C-reactive protein (C-reactive protein, p = 0.0001), and tumor necrosis factor alpha (TNFα, p = 0.0001). Overall, the observed effect sizes were small and the association of the Hannum residual with inflammatory markers was attenuated by adjustment for estimated T cell type percentages.ConclusionsOur study demonstrates that epigenetic age acceleration in blood relates to inflammatory biomarkers and certain lipid classes in Caucasian individuals of the GOLDN study. Future studies should consider epigenetic age acceleration in other tissues and extend the analysis to other ethnic groups.

An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial AUI response to FFB (P = 1.88E-06), respectively. We sought to replicate the association for SIPA1L2 in the Heredity and Phenotype Intervention (HAPI) Heart Study, which included a high-fat meal challenge but not FFB treatment. The associated rare variants in GOLDN were not observed in the HAPI Heart study, and thus the gene-based result was not replicated. For functional validation, we found that gene transcript level of SIPA1L2 is associated with triglyceride postprandial AUI (P < 0.05) in GOLDN. Our study suggests unique genetic mechanisms contributing to the lipid response to the high-fat meal challenge and FFB therapy.

A case of severe acquired hypertriglyceridemia in a 7-year-old girl

We report a case of severe type I hyperlipoproteinemia caused by autoimmunity against lipoprotein lipase (LPL) in the context of presymptomatic Sjögren's syndrome. A 7-year-old mixed race (Caucasian/African American) girl was admitted to the intensive care unit at Vanderbilt Children's Hospital with acute pancreatitis and shock. She was previously healthy aside from asthma and history of Hashimoto's thyroiditis. Admission triglycerides (TGs) were 2191 mg/dL but returned to normal during the hospital stay and in the absence of food intake. At discharge, she was placed on a low-fat, low-sugar diet. She did not respond to fibrates, prescription fish oil, metformin, or orlistat, and during the following 2 years, she was hospitalized several times with recurrent pancreatitis. Except for a heterozygous mutation in the promoter region of LPL, predicted to have no clinical significance, she had no further mutations in genes known to affect TG metabolism and to cause inherited type I hyperlipoproteinemia, such as APOA5, APOC2, GPIHBP1, or LMF1. When her TG levels normalized after incidental use of prednisone, an autoimmune mechanism was suspected. Immunoblot analyses showed the presence of autoantibodies to LPL in the patient's plasma. Autoantibodies to LPL decreased by 37% while patient was on prednisone, and by 68% as she subsequently transitioned to hydroxychloroquine monotherapy. While on hydroxychloroquine, she underwent a supervised high-fat meal challenge and showed normal ability to metabolize TG. For the past 3 years and 6 months, she has had TG consistently <250 mg/dL, and no symptoms of, or readmissions for, pancreatitis.

Dietary factors associated with high fat meal challenge based metabolic flexibility in women with metabolic syndrome

ObjectiveThe primary aim was to assess metabolic flexibility as it relates to habitual diet, as well as in response to a high fat meal challenge (HFMC).MethodsThirty‐three women with insulin resistance and/or dyslipidemia were enrolled in this study. Block food frequency 2014 questionnaire was used to evaluate habitual dietary patterns. A HFMC test (800 kcal, 60% fat, 25% cho, 15% pro) was provided in a protocol that included blood sampling and measures of O2 and CO2 exchange using a metabolic cart at fasting and at 30, 180 and 360 minutes postprandial. Metabolic rate (MR), respiratory exchange ratio (RER), fat (FOx) and carbohydrate (COx) oxidation rates were calculated from metabolic cart data. Food quotients (FQ) for habitual diets and the HFMC were calculated. Metabolic flexibility was assessed in the fasted state by comparing the FQ of the habitual diet with fasting RER (FQDIET/RERf). In the postprandial state, metabolic flexibility was defined as a ratio of [difference between average postprandial FOx and fasting FOx]/[difference between average postprandial COx and fasting COx] (ΔFOx/ΔCOx) and also the HFMC‐FQ compared to postprandial RER (FQHFMC/RERHFMC). Higher values for FQDIET/RERf, ΔFOx/ΔCOx, and FQHFMC/RERHFMC indicate higher FOx relative to COx. Spearman's correlation analysis was used to evaluate associations between dietary variables and metabolic flexibility.ResultsThree women were outliers (with reported dietary intake &gt; 4000 Kcal/d), and the remaining 30 women were included for analysis. ΔFOx/ΔCOx was inversely associated with resting MR (r = −0.444, p =0.010), and showed an inverse trend with omega‐3 fatty acid 20:4 (r = −0.33, p = 0.07). FQDIET/RERf similar to ΔFOx/ΔCox, showed an inverse trend with omega‐3 fatty acid 20:5 and 22:6 intakes (r = −0.31, p = 0.09, r = −0.33, p = 0.07). Similarly, FQHFMC/RERHFMC also showed an inverse trend with 20:5 and 22:6 (r = −0.33, p = 0.07 for both). It is of interest to note that while both FQDIET/RERf and FQHFMC/RERHFMC were positively associated with habitual caffeine intake (r = 0.53, p&lt;0.01, r = 0.39, p = 0.03), ΔFOx/ΔCOx was not (r =−0.15, p = 0.43). Also, both FQDIET/RERf and FQHFMC/RERHFMC were positively associated with habitual intake of flavanones (r = 0.37, p = 0.05; r = 0.35, p = 0.06), specifically hesperetin intake (r = 0.41, p = 0.03; r = 0.38, p = 0.04).ConclusionsMetabolic flexibility based on fasting measures was associated with lower intake of some long chain omega‐3 fatty acids, and higher intake of caffeine and flavanones in women. Higher intakes of omega‐3 fatty acids also indicated poorer adaptation to the HFMC. However, these must be tested in a larger sample size, as well as in a controlled feeding trial.Support or Funding InformationNational Dairy Council Project 23370, and USDA‐ARS‐CRIS Project 2032‐51530‐022‐00D

Abstract P106: Epigenetic Age Acceleration and Postprandial Lipemia in the Genetics of Lipid Lowering Drugs and Diet Network Study

Background: Calculated ‘epigenetic age,’ a novel biomarker based on DNA methylation levels of 353 CpGs, has been demonstrated to accurately predict chronological age across a broad spectrum of tissues and cell types. Recently epigenetic age acceleration or older epigenetic age in comparison to chronological age has been robustly associated with all-cause mortality independent of chronological age in multiple human cohorts. However, accelerated epigenetic aging has not been associated with lipids levels, including postprandial lipid levels which are linked to prothrombotic and proinflammatory processes that may precipitate aging. In the current study we aimed to evaluate the association between epigenetic age acceleration and lipid levels. Methods: We used the Horvath DNA methylation age calculator to estimate epigenetic age in 988 Caucasian participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) using Illumina Infinium HumanMethylation450 BeadChip array data derived from CD4+ T-cell DNA. GOLDN participants did not take lipid lowering drugs for at least four weeks prior to enrollment and underwent a standardized high fat meal challenge after fasting for at least 8 hours followed by timed blood draws at 3.5 and 6 hours following the meal. Epigenetic age acceleration was calculated as the residual from regressing methylation age on chronological age. We used linear mixed models to examine the association of age acceleration quartiles with fasting and postrandial (3.5 and 6 hour time points) low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG) levels after adjusting for age, study site, sex, fasting lipid level (if applicable), deconvolution estimated T-cell type percentages and a random effect of family relationship. Results: The correlation between calculated methylation age and chronological age was 0.91. The difference between methylation age and chronological age (methylation age - chronological age) was on average -5.8 (5.9), -0.5 (4.7), 2.9 (4.3), and 7.8 (5.0) years for the first through fourth quartiles of age acceleration, respectively. After adjustment for covariates neither fasting nor postprandial lipids were associated with age acceleration quartile. Conclusions: Evidence from the current study suggests lipid levels in the fasting and postprandial state are not related to accelerated epigenetic aging, however given the association between epigenetic age acceleration and mortality observed in previous studies the relationship of other metabolic parameters with age acceleration may be worthy of investigation.

Caloric dose-responsive genes in blood cells differentiate the metabolic status of obese men

We have investigated the postprandial transcriptional response of blood cells to increasing caloric doses of a meal challenge to test whether the dynamic response of the human organism to the ingestion of food is dependent on metabolic health.The randomized crossover study included seven normal weight and seven obese men consuming three doses (500/1000/1500 kcal) of a high-fat meal. The blood cell transcriptome was measured before and 2, 4, and 6 h after meal ingestion (168 samples). We applied univariate and multivariate statistics to investigate differentially expressed genes in both study groups.We identified 624 probe sets that were up- or down-regulated after the caloric challenge in a dose-dependent manner. These transcripts were most responsive to the 1500 kcal challenge in the obese group and were associated with postprandial insulin and oxidative phosphorylation. Furthermore, the data revealed a separation of the obese group into individuals whose response was close to the normal weight group and individuals with a transcriptional response indicative of a loss of metabolic flexibility.The molecular signature provided by the postprandial transcriptomic response of blood cells to increasing caloric doses of a high-fat meal challenge may represent a sensitive way to evaluate the qualitative impact of food on human health.

Consumption of a flavonoid-rich açai meal is associated with acute improvements in vascular function and a reduction in total oxidative status in healthy overweight men

Açai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from açai consumption in humans is limited. The objective of the present study was to investigate the effect of açai consumption on acute changes in vascular function and on other disease risk markers, including postprandial plasma insulin, glucose, and oxidative stress. Twenty-three healthy male volunteers, aged 30-65 y and with a body mass index (in kg/m2) of 25-30, completed a randomized, controlled, high-fat challenge, double-blind, crossover, acute dietary intervention trial. The volunteers consumed either an açai-based smoothie (AS) or a macronutrient-matched control smoothie (PS) together with a high-fat breakfast meal challenge. The primary endpoint was the assessment of endothelial function in the brachial artery by flow-mediated dilatation (FMD). The acute consumption of an AS containing 694 mg total phenolics improved vascular function, with postprandial increases in FMD from baseline of 1.4% at 2 h compared with 0.4% after consumption of the PS (P = 0.001) and increases at 6 h of 0.8% for the AS compared with -0.3% for the PS (P < 0.001). There was also a significantly lower incremental area under the curve (iAUC) for total peroxide oxidative status after açai consumption relative to the control. No significant changes were observed in blood pressure, heart rate, or postprandial glucose response. However, the first postprandial insulin peak (after breakfast) and the iAUC for insulin were elevated for the AS relative to the PS. In this acute study in overweight men, açai consumption was associated with improvements in vascular function, which may lower the risk of a cardiovascular event. Future intervention studies, perhaps with a chronic design, in wider populations and with other biomarkers of disease risk are needed to fully elucidate the benefits of açai to health. This trial was registered at clinicaltrials.gov as NCT02292329.

Impairment of lysophospholipid metabolism in obesity: altered plasma profile and desensitization to the modulatory properties of n–3 polyunsaturated fatty acids in a randomized controlled trial

Plasma lysophospholipids have emerged as signaling molecules with important effects on inflammation, insulin resistance, and fatty liver disease, each of which is linked closely to obesity. Dietary n-3 (ω-3) polyunsaturated fatty acids (PUFAs) may be able to improve these conditions. The objective of this study was to assess the response of plasma lysophospholipids to obesity, n-3 PUFA consumption, and a high-fat meal challenge to better understand the role of lysophospholipid metabolism in the progression of obesity-related disorders. We determined the concentrations of 8 lysophosphatidylcholines, 11 lysophosphatidylethanolamines, and 7 lysophosphatidylinositols in the plasma of 34 normal-weight and 38 obese subjects randomly assigned to consume corn oil (control) or n-3 PUFA-rich fish oil (3 g/d; n = 15-19/group) for 90 d. Blood samples were collected on the last day of the study under fasting conditions and 6 h after a high-fat meal (1135 kcal, 86 g fat) challenge. The profile of secreted lysophospholipids was studied in HepG2 cells under palmitate-induced steatosis. Obese and normal-weight subjects had different profiles of plasma lysophospholipids. A multivariate combination of the 26 lysophospholipids could discriminate between normal-weight and obese subjects with an accuracy of 98%. The high-fat meal challenge altered the concentration of plasma lysophosphatidylcholines in an oil treatment-dependent manner in normal-weight but not obese subjects, suggesting that obesity impairs the sensitivity of lysophospholipid metabolism to n-3 PUFAs. Noncytotoxic steatosis in HepG2 cells affected the secretion pattern of lysophospholipids, partially resembling the changes observed in the plasma of obese subjects. Obesity has a substantial impact on lysophospholipid metabolism, altering the plasma lysophospholipid profile and abolishing its sensitivity to dietary n-3 PUFAs. These effects could contribute to the onset or progression of alterations associated with obesity, such as inflammation, insulin resistance, and fatty liver disease. This trial was registered at www.controlled-trials.com as ISRCTN96712688.

Processed tomato products and risk factors for cardiovascular disease

BACKGROUND: Lipids, inflammation, oxidative stress and elevated blood pressure are targets for lowering cardiovascular disease (CVD) risk with a healthy diet. OBJECTIVE: We tested the effect of tomato products, dietary sources of lycopene and potassium, on changes in lipids/lipoproteins, inflammation and blood pressure. METHODS: In a two-center, randomized, parallel, controlled trial, processed tomato or non-tomato products matched in energy, sodium, and sugar content (HT = high tomato, 5 servings/day vs LT = low tomato/control, <1 serving/day, respectively) were included in the diets of free-living overweight men and women 21 to 70 years of age (n= 53) for 6 weeks. All subjects had a 3-week LT run-in followed by either 6-week HT or LT/control diet. A random subset of 23 subjects had 2 postprandial (6 hour) visits at weeks 0 and 6 to assess the enduring effects of the HT vs LT diets on high fat meal-induced changes in lipids, insulin, glucose, inflammation, and blood pressure. RESULTS: Fasting lipids/lipoproteins, insulin, glucose and C-reactive protein did not differ between the HT vs LT diets after 6 weeks intervention. Diastolic blood pressure was significantly decreased on the HT diet after 6 weeks compared to baseline, week 0 (p= 0.02) and compared to LT at week 6 (p= 0.03). Systolic blood pressure was not different between treatments at 6 weeks (p= 0.11). Tomato-associated effect sizes on blood pressure were greater in a sub-set of subjects with elevated blood pressure but were not statistically powered to reveal a significant effect between LT and HT treatments; however, the effect on lowering diastolic blood pressure remained, p< 0.05 compared to baseline). Chronic intervention with processed tomatoes did not impact postprandial glucose, insulin, lipids or inflammatory marker responses to a high fat meal challenge at the end of the study (n= 23). CONCLUSIONS: Processed tomatoes decreased diastolic blood pressure, but had no significant effects on other endpoints. Future research is required to confirm and potentially extend these findings in individuals with elevated blood pressure.

Identification of a botanical inhibitor of intestinal diacylglyceride acyltransferase 1 activity via in vitro screening and a parallel, randomized, blinded, placebo-controlled clinical trial.

BackgroundDiacylglyceride acyltransferase 1 (DGAT1) is the enzyme that adds the final fatty acid on to a diacylglyceride during triglyceride (TG) synthesis. DGAT1 plays a key role in the repackaging of dietary TG into circulating TG rich chylomicrons. A growing amount of research has indicated that an exaggerated postprandial circulating TG level is a risk indicator for cardiovascular and metabolic disorders. The aim of this research was to identify a botanical extract that inhibits intestinal DGAT1 activity and attenuates postprandial hypertriglyceridemia in overweight and obese humans.MethodsTwenty individual phytochemicals and an internal proprietary botanical extract library were screened with a primary cell-free DGAT1 enzyme assay that contained dioleoyl glycerol and palmitoleoyl Coenzyme A as substrates plus human intestinal microsomes as the DGAT1 enzyme source. Botanical extracts with IC50 values < 100 μg/mL were evaluated in a cellular DGAT1 assay. The cellular DGAT1 assay comprised the analysis of 14C labeled TG synthesis in cells incubated with 14C-glycerol and 0.3 mM oleic acid. Lead botanical extracts were then evaluated in a parallel, double-blind, placebo-controlled clinical trial. Ninety healthy, overweight and obese participants were randomized to receive 2 g daily of placebo or individual botanical extracts (the investigational product) for seven days. Serum TG levels were measured before and after consuming a high fat meal (HFM) challenge (0.354 L drink/shake; 77 g fat, 25 g carbohydrate and 9 g protein) as a marker of intestinal DGAT1 enzyme activity.ResultsPhenolic acids (i.e., gallic acid) and polyphenols (i.e., cyanidin) abundantly found in nature appeared to inhibit DGAT1 enzyme activity in vitro. Four polyphenolic rich botanical extracts were identified from in vitro evaluation in both cell-free and cellular model systems: apple peel extract (APE), grape extract (GE), red raspberry leaf extract (RLE) and apricot/nectarine extract (ANE) (IC50 = 1.4, 5.6, and 10.4 and 3.4 μg/mL, respectively). In the seven day clinical trial, compared to placebo, only GE significantly reduced the baseline subtracted change in serum TG AUC following consumption of the HFM (AUC = 281 ± 37 vs. 181 ± 30 mg/dL*h, respectively; P = 0.021). Chromatographic characterization of the GE revealed a large number of closely eluting components containing proanthocyanidins, catechins, anthocyanins and their secondary metabolites that corresponded with the observed DGAT1 enzyme inhibition in the cell-free model.ConclusionThese data suggest that a dietary GE has the potential to attenuate postprandial hypertriglyceridemia in part by the inhibition of intestinal DGAT1 enzyme activity without intolerable side effects.Trial registrationThis trial was registered with ClinicalTrials.gov NCT02333461Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-015-0025-2) contains supplementary material, which is available to authorized users.

Short-term high-fat diet increases postprandial trimethylamine-N-oxide in humans

The gut microbiota plays an obligatory role in the metabolism of nutrients containing trimethylamine moieties, such as l-carnitine and choline, leading to the production of the proatherogenic trimethylamine-N-oxide (TMAO). We hypothesized that a short-term, high-fat diet would increase fasting and postprandial plasma concentrations of TMAO in response to a high-fat meal challenge. Following a 2-week eucaloric control diet, 10 nonobese men (18-30 years) consumed a eucaloric, high-fat diet (55% fat) for 5 days. Plasma TMAO was measured after a 12-hour fast and each hour after for 4 hours following a high-fat meal (63% fat) at baseline and after the high-fat diet using ultraperformance liquid chromatography/ tandem mass spectrometry. Fasting plasma TMAO did not increase significantly following the high-fat diet (1.83 ± 0.21 vs 1.6 ± 0.24 μmol/L). However, plasma TMAO was higher at hour 1 (2.15 ± 0.28 vs 1.7 ± 0.30 μmol/L), hour 2 (2.3 ± 0.29 vs 1.8 ± 0.32 μmol/L), hour 3 (2.4 ± 0.34 vs 1.58 ± 0.19 μmol/L), and hour 4 (2.51 ± 0.33 vs 1.5 ± 0.12 μmol/L) (all P < .05) following the high-fat diet as compared with the baseline postprandial response. In conclusion, a short-term, high-fat diet does not increase fasting plasma TMAO concentrations but appears to increase postprandial TMAO concentrations in healthy, nonobese, young men. Future studies are needed to determine the mechanisms responsible for these observations.

Acute and Chronic Effects of Sprint Interval Training on Postprandial Lipemia in Women At‐Risk for Metabolic Syndrome

Individuals with the metabolic syndrome (MetS) exhibit elevated postprandial triglycerides (TG). The aims of this investigation were to determine 1) the effectiveness of 6 weeks of sprint interval training (SIT) on postprandial lipemia (PPL) and 2) if the attenuation of PPL following 6‐weeks of SIT is magnified compared to a single session of SIT prior to training in women at‐risk for MetS (n = 45; 30‐65 yrs). Postprandial responses to a high‐fat meal challenge (HFMC) were assessed for 3 h at baseline (B‐HFMC; all participants) without prior exercise, paired with a single session of SIT (four 30‐s all‐out sprints with 4‐min recovery) prior to the intervention (Pre‐HFMC; SIT only), and after the 6‐week SIT intervention without prior exercise (Post‐HFMC; CON) or paired with an acute bout of SIT ~14‐18 h prior to Post‐HFMC (SIT). Responses to the HFMC were assessed by collecting venous blood samples fasted and at 0, 30, 60, 120, and 180 min postprandial. Compared to baseline, an acute bout of SIT before (Pre‐HFMC) and after the 6‐week intervention (Post‐HFMC) significantly attenuated fasted (P&lt;0.05; 16.6% and 12.3%, respectively) and postprandial area under the curve (13.1% and 9.7%, respectively; tAUC) TG responses. There was no difference in fasted or tAUC TG responses between Pre‐HFMC and Post‐HFMC. SIT is an effective mode of exercise to reduce fasting and postprandial TG concentrations in women at‐risk for MetS.

Acute and chronic effects of sprint interval exercise on postprandial lipemia in women at-risk for the metabolic syndrome.

Individuals diagnosed with the metabolic syndrome (MetS) exhibit elevated postprandial lipemia (PPL). The aims of this investigation were to determine 1) if an acute bout of sprint interval training (SIT) attenuates PPL; and 2) if the attenuation of PPL following 6 wk of SIT is magnified compared with a single session of SIT prior to training in women at-risk for MetS (n = 45; 30-65 yr). Women were randomized to SIT (n = 22) or a nonexercise control (n = 23; CON) for 6 wk. Postprandial responses to a high-fat meal challenge (HFMC) were assessed in the CON group before (B-HFMC) and after (Post-HFMC) without prior exercise and in the SIT group at baseline (B-HFMC) without prior exercise, after an acute bout of SIT (four 30-s all-out sprints with 4-min recovery) prior to (Pre-HFMC), and after the 6-wk intervention (Post-HFMC). Responses to the HFMC were assessed by collecting venous blood samples in the fasted state and at 0, 30, 60, 120, and 180 min postprandial. Compared with baseline, an acute bout of SIT before (Pre-HFMC) and after the 6-wk intervention (Post-HFMC) significantly attenuated fasted TG (P < 0.05; 16.6% and 12.3%, respectively) and postprandial area under the curve (13.1% and 9.7%, respectively; tAUC) TG responses. There was no difference in fasted or tAUC TG responses between Pre-HFMC and Post-HFMC. SIT is an effective mode of exercise to reduce fasted and postprandial TG concentrations in women at-risk for MetS. Six weeks of SIT does not magnify the attenuation of PPL in response to a single session of SIT.

Predicting Postprandial Oxidative Stress Using Serum Triglycerides Following Oral Fat Tolerance Testing

Background: The topic of postprandial oxidative stress continues to receive considerable attention, with elevations in oxidative stress biomarkers associated with human disease (e.g., insulin resistance, atherosclerosis). The predictable rise in serum triglyceride (TAG) following high fat meal ingestion is strongly correlated to the increase in circulating oxidative stress biomarkers. Our intent with the present study was two-fold: 1) To further characterize the postprandial response to high fat feeding and 2) to develop regression models that could be used to predict the oxidative stress response to high fat feeding. Methods: 154 men and women reported to the lab in the morning hours following an overnight fast and consumed a high fat liquid meal. Blood samples were collected before meal ingestion and at 2 and 4 hours following meal ingestion. Samples were analyzed for TAG and oxidative stress biomarkers (hydrogen peroxide [H2O2], malondialdehyde [MDA], advanced oxidation protein Original Research Article Bloomer et al; BJMMR, 5(12): 1514-1526, 2015; Article no.BJMMR.2015.171 1515 products [AOPP]). Simple linear regression analyses were used for model development to predict the oxidative stress response to feeding. In addition, biochemical variables were analyzed using an analysis of variance (ANOVA) to present response to feeding data across time. Results: In all of the regression models, TAG explained a significant portion of the outcome variables (H2O2, MDA, and AOPP) and predictor models were created for each variable. In addition, values for TAG and all oxidative stress biomarkers increased following meal ingestion. A time effect was noted where all values were higher post meal ingestion as compared to pre meal for all biochemical variables (p<0.05). Conclusion: Obtaining serum TAG values in response to a high fat meal challenge may provide investigators with the ability to predict postprandial oxidative stress using regression equations.

A 3-month low fat diet leads to significant lipid profile improvement in obese T2DM Saudi subjects, without substantial weight loss, and the capacity to manage a damaging high-fat meal challenge more appropriately post intervention

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Vascular consequences of a high-fat meal in physically active and inactive adults

Habitually active adults (ACT) typically exhibit lower postprandial lipemia, a condition that may attenuate oxidative stress and endothelial dysfunction following a high-fat meal (HFM), compared with inactive adults (INA). Our objective was to compare triglycerides (TAG), superoxide dismutase activity (SOD), oxidative stress (thiobarbituric reactive substances; TBARS), and brachial artery flow-mediated dilation (FMD%) before and after an HFM challenge in ACT and INA. ACT (n = 7) and INA (n = 7) subjects were matched for body mass index, age, and sex. Plasma TAG, SOD, TBARS, and FMD% were measured at baseline and 4 h after an HFM challenge. TAG significantly increased following the HFM in INA (4.15± 3.79mmol·L(-1) vs. 8.07± 5.12 mmol·L(-1)) and in ACT (2.16± 0.55mmol·L(-1) vs. 3.24± 1.40mmol·L(-1)). Baseline TBARS were greater in ACT and remained unchanged in response to the HFM in both INA (5.1± 2.7mmol·L(-1) vs. 6.9± 2.9mmol·L(-1)) and ACT (8.6± 2.0mmol·L(-1) vs. 7.9± 1.9mmol·L(-1)). ACT exhibited greater SOD than INA at baseline (8.6± 0.7 U·mL(-1) vs. 7.8± 0.6 U·mL(-1)) and following the HFM (9.3± 1.2 U·mL(-1) vs. 8.0± 0.7 U·mL(-1)). Postprandial FMD% was decreased in INA (9.1%± 4.0% vs. 6.2%± 3.4%), yet remained unchanged in ACT (7.9%± 3.7% vs. 9.3%± 3.2%). In conclusion, the differential responses following an HFM support the concept that habitual physical activity can attenuate the negative postprandial alterations that affect vascular health.

Apolipoprotein E Polymorphisms and Postprandial Triglyceridemia Before and After Fenofibrate Treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) Study

Although much is known about the effect of Apolipoprotein E (APOE) alleles on fasting lipid concentrations, less is known about the effect of APOE alleles on postprandial triglyceridemia or the triglyceride response to fenofibrate. We evaluated the effects of the APOE locus on fasting and postprandial triglyceride concentrations as part of the Genetics of Lipid Lowering and Diet Network (GOLDN) study. Participants were evaluated after a high-fat meal challenge before (n=1072) and after 3 weeks of daily treatment with 160 mg of fenofibrate (n=738). Mixed models adjusted for sex, age, waist circumference, and family relationship were used to examine the association of the ε4 carrier and ε2 carrier status versus ε3 homozygotes with fasting triglycerides and the area under the curve (AUC) for triglycerides during the high-fat meal challenge. Compared with the ε3/ε3 genotype, ε2 carriers had on average higher fasting triglyceride concentrations (130.5 mg/dL versus 109.3 mg/dL, P<0.001). After fenofibrate treatment, the APOE genotype differences persisted in the fasting state (ε2 carriers: 85.1 mg/dL versus ε3/ε3: 75.9 mg/dL, P<0.05). Carriers of the ε4 allele had significantly higher fasting triglyceride concentrations only prefenofibrate (120.9 mg/dL versus 109.3 mg/dL, P=0.008). APOE alleles did not have an effect on response to fenofibrate. Postprandial triglycerides were significantly higher for ε2 carriers versus ε3 homozygotes (but not ε4 carriers) both before and after fenofibrate treatment (P=0.01 and P=0.005, respectively). APOE polymorphisms are important determinants of triglyceride concentrations, especially in the fasting state.

Fitness And Body Composition Do Not Affect Racial Differences In Endothelial Function In Postmenopausal Women

Endothelial dysfunction is a known predictor of cardiovascular disease (CVD), and may be worsened in the postprandial state, particularly after ingestion of a high-fat meal. In women, postmenopausal status increases the risk of endothelial dysfunction, which tends to be more impaired in African Americans (AA). Low aerobic fitness and obesity are also associated with impaired endothelial function. PURPOSE: We investigated whether fitness and fatness affected endothelial function at rest and after a high-fat meal challenge in AA and Caucasian (C) postmenopausal women matched for age, BMI, % fat and VO2peak. METHODS: We were able to match 8 AA and 8 C (Age= 55.0 + 1.7 vs 57.6 + 5.2 yr; BMI= 30.8 vs 29.3 kg/m2; %fat 43.4 vs 43.2%; VO2peak= 22.1 vs 21.5 ml/kg/min) subject pairs from a larger sample of postmenopausal women enrolled in a training study. Each subject underwent a VO2peak treadmill protocol, % fat assessment by air displacement plethysmography, and brachial artery flow-mediated dilation (FMD) measurements at baseline, and 2 and 4-hours after a high-fat meal (57% FAT, 25% PROT,18% CHO). Percent FMD was quantified by comparing B-mode ultrasound images of the brachial artery at rest and during reactive hyperemia after 5 min of forearm occlusion. RESULTS: Mixed-model ANOVA revealed impaired postprandial FMD in AA. Baseline FMD was similar between AA and C (5.1% + 2.5 vs 4.3% + 3.4, p= 0.197). In contrast, 2h FMD was reduced in AA (3.5%) and increased in C (9.8%) (p<0.001 AA vs C). At 4h, similar FMD values were observed (AA=6.0% + 2.7, C=6.8% + 3.1). CONCLUSIONS: The present data suggest that the postprandial impairment in FMD observed in postmenopausal AA women compared to C is independent of fitness and body composition. Supported by NIH grant RR00847 to the GCRC