Single High-fat Meal Research Articles

The impact of a single high-fat meal on indices of cerebrovascular function & health

High-fat diets contribute to elevated risk for cardiovascular, cerebrovascular, metabolic, and neurocognitive diseases with reduced vascular health being a contributing factor. It is well documented that a single high-fat meal (HFM) reduces peripheral vascular function. Despite the elevated risk for/prevalence of cerebrovascular and neurocognitive disease with a high-fat diet, the impact of a single HFM on cerebrovascular function/health is less known. Cerebrovascular pulsatility index (PI) (measure of cerebral vascular stiffness) and cerebral autoregulation (ability of the cerebral vasculature to maintain constant blood flow during changes in arterial blood pressure) are indices of cerebral vascular function/health that are impaired in populations with elevated disease risk. To our knowledge, the impact of a HFM on these indices have not been studied. Accordingly, this study tested the hypothesis that a single HFM will blunt cerebrovascular function/health as indexed by increased PI and transfer function gain. Methods: Fifteen individuals (13 male; age: 28±11yr; BMI: 24±4 kg/m²) participated. Measures were made before and 2hr post-consumption of a HFM (990 kcal, 55g fat, 89g CHO, 35 g protein, 2120 mg sodium) which was purchased from McDonald’s. The HFM consisted of the following: 1 Sausage Biscuit, 1 Egg McMuffn, 2 hash browns, and 1 bottle of water. Continuous measures of beat-to-beat blood pressure and middle cerebral artery blood velocity (MCAV) were obtained during a minimum of 6-min quiet supine rest. Pulsatility index (measure of cerebrovascular stiffness) was calculated as MCAVsystolic − MCAVdiastolic / MCAVmean. Cerebral autoregulation was calculated as transfer function gain between spontaneous beat-to-beat changes in mean blood pressure and MCAVmean. Results: Cerebrovascular stiffness (PI) was increased following the HFM (pre: 0.81±0.12, post: 0.92±0.15; p<0.001). Cerebrovascular autoregulation indexed as transfer function gain was elevated following the HFM in the very low, low, and high frequency ranges ( p=0.01 for all). Pulsatility index and transfer function gain were correlated in the low frequency range before (R=0.77, p<0.01) and after (R=0.64, p=0.02) the HFM. Conclusion: These preliminary data indicate that a single HFM reduces indices of cerebral vascular function/health. Lastly, there is a positive relationship between PI and transfer function gain. Future work will continue to build upon these findings in a larger data set and will consider the impact of long-term exposure to a traditional HFM diet. Funding: The University of Texas at Arlington College of Nursing and Health Innovation and Institutional Start up Funds to Dr. Brothers. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A single high-fat Western meal modulates vascular responsiveness to sympathetic activation at rest and during exercise in humans: a randomized controlled trial.

A single high-fat Western meal transiently reduces endothelium-dependent vasodilation at rest but the interaction with sympathetic vasoconstrictor activity during exercise remains unknown. Herein, we tested the hypothesis that a single high-fat Western meal would impair the ability of contracting skeletal muscle to offset vascular responsiveness to sympathetic activation during exercise, termed functional sympatholysis. In 18 (10F/8M) healthy young adults, forearm blood flow (Doppler ultrasound) and beat-to-beat arterial pressure (photoplethysmography) were measured during lower-body negative pressure (LBNP; -20 mmHg) applied at rest and simultaneously during low- (15% maximum contraction) and moderate-intensity (30% maximum contraction) rhythmic handgrip. The magnitude of sympatholysis was calculated as the difference of LBNP-induced changes in forearm vascular conductance (FVC) between handgrip and rest. Experiments were performed preprandial and 1h, 2h, and 3h after a high- or low-fat meal. In the preprandial state, LBNP decreased resting FVC (∆-54±10%), and these responses were attenuated during low- (∆-17±7%) and moderate-intensity handgrip (∆-8±6%). Following a high-fat meal, LBNP induced attenuated decreases in resting FVC (3h postprandial: ∆-47±10%, P=0.002 vs. preprandial), and blunted attenuation of FVC during low- (3h postprandial: ∆-23±8%, P=0.001 vs. preprandial) and moderate-intensity handgrip (3h postprandial: ∆-16±6%, P<0.001 vs. preprandial). The high-fat meal attenuated the magnitude of sympatholysis during low- (preprandial: 38±7% vs. 3h postprandial: 23±8%, P<0.001) and moderate-intensity handgrip (preprandial: 46±11% vs. 3h postprandial: 31±10%, P<0.001). The low-fat meal had no impact on these responses. In conclusion, a single high-fat Western meal modulates sympathetic vasoconstriction at rest and during low- and moderate-intensity handgrip exercise in young healthy adults.

The Effect of Varying Fatty Acid Composition on Postprandial Airway Inflammation, Pulmonary Function, and Airway Resistance in Healthy, Young Adults

The Western Diet commonly consists of high-fat meals (HFMs) with saturated fats (SF) and increased omega-6 polyunsaturated fatty acids (O6FA) to omega-3 polyunsaturated fatty acids (O3FA) ratios. Even a single high-fat meal (HFM) may increase airway inflammation assessed via exhaled nitric oxide (eNO). When HFMs are consumed chronically, persistent airway inflammation may lead to deleterious structural changes in the airways, decrease pulmonary function, and increase the risk of respiratory disease development. Objective To examine the effect of varying fatty acid composition in a HFM on eNO, pulmonary function, and airway resistance. Methods Fifteen individuals [6 M/9 F; 21.9 ± 1.5 years old] each completed three HFM conditions {SF, O6FA, and O3FA; 12 kcal/kg body weight, 63% total fat, and 0.72 g/kg sugar smoothies} in random order separated by at least 48 h. Airway inflammation assessed via eNO, pulmonary function measured using the maximum flow volume loop (MFVL) and airway resistance measured using impulse oscillometry (iOS) were taken at baseline, 2h and 4h postprandially. Results There was no difference in eNO or iOS across time in any condition or between conditions (p > 0.05). There was a significant time by condition effect for FEV1 post-HFM in the SF and O6FA conditions (p < 0.05). Conclusion Different fatty acid compositions do not increase eNO or iOS in healthy, college-aged participants after consumption of a HFM, though the minimally processed meals with fruit added may contribute to these findings.

A single high-fat meal impairs functional sympatholysis in young healthy adults

Introduction: A high-fat diet increases the risk of cardiovascular disease and mortality, but the underlying mechanisms remain incompletely understood. During exercise, sympathetically mediated vasoconstriction is dampened in active skeletal muscle due to the counteracting vasodilatory effects of metabolic by-products from muscle contraction. This phenomenon, termed functional sympatholysis, plays a critical role in the redistribution of cardiac output to contracting skeletal muscles to meet the metabolic demands of exercise. Whether a high-fat meal modulates the magnitude of sympatholysis is currently unknown. Herein, we tested the hypothesis that a high-fat meal would acutely impair functional sympatholysis in young healthy adults. Methods: In a randomized, controlled, and cross-over design, 14 healthy adults (8 women, 26±4 years), consumed either a high- (1030kcals, 91g fat) or a low-fat (1006kcals, 1g fat) meal on two separate days. Forearm blood flow (FBF; Doppler ultrasound) and beat-to-beat mean arterial pressure (MAP; finger photoplethysmography) were measured during sympathetic activation induced by -20 mmHg lower-body negative pressure (LBNP) applied at rest and simultaneously during rhythmic handgrip exercise at 15% and 30% maximum voluntary contraction (MVC). Measurements were taken pre-meal and at 1-, 2-, and 3-hours post-prandial. Forearm vascular conductance (FVC) was calculated as FBF/MAP and the magnitude of sympatholysis as the difference of LBNP-induced changes in FVC between handgrip and rest. Results: Prior to the high-fat meal, LBNP decreased resting FVC (Δ-57±10%), and this response was attenuated during exercise at 15% (Δ-18±8%) and 30% MVC (Δ-9±7%). After the high-fat meal, LBNP induced smaller decreases in resting FVC (1h: Δ-43±12%, 2h: Δ-45±12%, 3h: Δ-49±8%, all P≤0.01 vs. pre), but during exercise greater decreases in FVC were observed at both 15% (1h: Δ-22±10%, 2h: Δ-23±8%, 3h: Δ-25±8%, all P≤0.04 vs. pre) and 30% MVC (1h: Δ-15±8%, 2h: Δ-15±6%, 3h: Δ-16±6%, all P≤0.04 vs. pre). As a result, the high-fat meal decreased the magnitude of sympatholysis during rhythmic handgrip exercise at 15% (pre-prandial: 39±8%, 1h: 20±10%, 2h: 21±8%, 3h: 24±7%, all P≤0.001) and 30% MVC (pre-prandial: 48±11%, 1h: 28±10%, 2h: 30±11%, 3h: 33±8%, all P≤0.001). The low-fat meal did not change the magnitude of sympatholysis at either 15% (pre-prandial: 37±6%, 1h: 39±6%, 2h: 38±7%, 3h: 37±8%, all P≥0.07) or 30% MVC (pre-prandial: 45±10%, 1h: 47±8%, 2h: 47±9%, 3h: 46±7%, all P≥0.39). Conclusion: These findings demonstrate the capacity of a high-fat meal to acutely impair the ability of contracting skeletal muscle to offset the vascular responsiveness to α1-adrenoreceptor activation during low- and moderate-intensity rhythmic handgrip exercise. Natural Science and Engineering Research Council (NSERC) of Canada Discovery Grant (P.J.M) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of a high-fat meal on inflammatory and endothelial injury biomarkers in accordance with adiposity status: a cross-sectional study

BackgroundIt is known that consuming a high-fat meal (HFM) induces microvascular dysfunction (MD) in eutrophic women and aggravates it in those with obesity. Our purpose was to investigate if the MD observed after a single HFM intake is caused by endothelial damage or increased inflammatory state, both determined by blood biomarkers.MethodsNineteen women with obesity (BMI 30-34.9 kg/m2) and 18 eutrophic ones (BMI 20.0-24.9 kg/m2) were enrolled into two groups: Obese (OBG) and Control (CG), respectively. Blood samples were collected at five-time points: before (fasting state) and 30, 60, 120, and 180 min after HFM intake to determine levels of adipokines (adiponectin, leptin), non-esterified fatty acid (NEFA), inflammatory [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)] and endothelium damage [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1)] biomarkers.ResultsLevels of soluble E-selectin, leptin, and PAI-1 were higher in OBG at all-time points (P < 0.05) compared to CG. In the fasting state, OBG had higher levels of NEFA compared to CG (P < 0.05). In intra-group analysis, no significant change in the levels of circulating inflammatory and endothelial injury biomarkers was observed after HFM intake, independently of the group.ConclusionOur findings suggest that women with obesity have an increased pro-inflammatory state and more significant endothelial injury compared to eutrophic ones. However, the consumption of a HFM was not sufficient to change circulating levels of inflammatory and endothelial injury biomarkers in either group.Registration number for clinical trials:NCT01692327.

African American Females Are Less Metabolically Flexible Compared with Caucasian American Females following a Single High-Fat Meal: A Pilot Study.

The relationship between metabolic flexibility (MF) and components of metabolic disease has not been well-studied among African American (AA) females and may play a role in the higher incidence of chronic disease among them compared with Caucasian American (CA) females. This pilot study aimed to compare the metabolic response of AA and CA females after a high-fat meal. Eleven AA (25.6 (5.6) y, 27.2 (6.0) kg/m2, 27.5 (9.7) % body fat) and twelve CA (26.5 (1.5) y, 25.7 (5.3) kg/m2, 25.0 (7.4) % body fat) women free of cardiovascular and metabolic disease and underwent a high-fat meal challenge (55.9% fat). Lipid oxidation, insulin, glucose, and interleukin (IL)-8 were measured fasted, 2 and 4 h postprandial. AA females had a significantly lower increase in lipid oxidation from baseline to 2 h postprandial (p = 0.022), and trended lower at 4 h postprandial (p = 0.081) compared with CA females, indicating worse MF. No group differences in insulin, glucose or HOMA-IR were detected. IL-8 was significantly higher in AA females compared with CA females at 2 and 4 h postprandial (p = 0.016 and p = 0.015, respectively). These findings provide evidence of metabolic and inflammatory disparities among AA females compared with CA females that could serve as a predictor of chronic disease in individuals with a disproportionately higher risk of development.

A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis

ABSTRACTBackgroundEndothelial dysfunction is a predictive risk factor for the development of atherosclerosis and is assessed by flow-mediated dilation (FMD). Although it is known that NO-dependent endothelial dysfunction occurs after consuming a high-fat meal, the magnitude of the effect and the factors that affect the response are unquantified.ObjectivesWe conducted a systematic review and meta-analysis exploring the quantitative effects of a single high-fat meal on endothelial function and determined the factors that modify the FMD response.MethodsSix databases were systematically searched for original research published up to January 2022. Eligible studies measured fasting and postprandial FMD following consumption of a high-fat meal. Meta-regression was used to analyze the effect of moderator variables.ResultsThere were 131 studies included, of which 90 were suitable for quantitative meta-analysis. A high-fat meal challenge transiently caused endothelial dysfunction, decreasing postprandial FMD at 2 hours [−1.02 percentage points (pp); 95% CI: −1.34 to −0.70 pp; P < 0.01; I2 = 93.3%], 3 hours [−1.04 pp; 95% CI: −1.48 to −0.59 pp; P < 0.001; I2 = 84.5%], and 4 hours [−1.19 pp; 95% CI: −1.53 to −0.84 pp; P < 0.01; I2 = 94.6%]. Younger, healthy-weight participants exhibited a greater postprandial reduction in the FMD percentage change than older, heavier, at-risk groups after a high-fat meal ( P < 0.05). The percentage of fat in the meals was inversely associated with the magnitude of postprandial changes in FMD at 3 hours (P < 0.01).ConclusionsA single, high-fat meal adversely impacts endothelial function, with the magnitude of the impact on postprandial FMD moderated by the fasting FMD, participant age, BMI, and fat content of the meal. Recommendations are made to standardize the design of future postprandial FMD studies and optimize interpretation of results, as high-fat meals are commonly used in clinical studies as a challenge to assess endothelial function and therapeutics. This trial was registered at PROSPERO as CRD42020187244.

Transcriptional Integration of Distinct Microbial and Nutritional Signals by the Small Intestinal Epithelium.

Background & AimsThe intestine constantly interprets and adapts to complex combinations of dietary and microbial stimuli. However, the transcriptional strategies by which the intestinal epithelium integrates these coincident sources of information remain unresolved. We recently found that microbiota colonization suppresses epithelial activity of hepatocyte nuclear factor 4 nuclear receptor transcription factors, but their integrative regulation was unknown.MethodsWe compared adult mice reared germ-free or conventionalized with a microbiota either fed normally or after a single high-fat meal. Preparations of unsorted jejunal intestinal epithelial cells were queried using lipidomics and genome-wide assays for RNA sequencing and ChIP sequencing for the activating histone mark H3K27ac and hepatocyte nuclear factor 4 alpha.ResultsAnalysis of lipid classes, genes, and regulatory regions identified distinct nutritional and microbial responses but also simultaneous influence of both stimuli. H3K27ac sites preferentially increased by high-fat meal in the presence of microbes neighbor lipid anabolism and proliferation genes, were previously identified intestinal stem cell regulatory regions, and were not hepatocyte nuclear factor 4 alpha targets. In contrast, H3K27ac sites preferentially increased by high-fat meal in the absence of microbes neighbor targets of the energy homeostasis regulator peroxisome proliferator activated receptor alpha, neighbored fatty acid oxidation genes, were previously identified enterocyte regulatory regions, and were hepatocyte factor 4 alpha bound.ConclusionsHepatocyte factor 4 alpha supports a differentiated enterocyte and fatty acid oxidation program in germ-free mice, and that suppression of hepatocyte factor 4 alpha by the combination of microbes and high-fat meal may result in preferential activation of intestinal epithelial cell proliferation programs. This identifies potential transcriptional mechanisms for intestinal adaptation to multiple signals and how microbiota may modulate intestinal lipid absorption, epithelial cell renewal, and systemic energy balance.

A Single High Fat Meal Adversely Affects Postprandial Endothelial Function: A Systematic Review and Meta-Analysis

Abstract Objectives High-fat diets are associated with endothelial dysfunction, the first step in the progression to atherosclerosis and cardiovascular disease. We aimed to determine the postprandial endothelial response (flow-mediated dilation (FMD)) to a high-fat meal in various populations and define how the response varies by conducting a systematic review of the literature. Methods Six electronic databases were systematically searched for original research published from database inception to May 2020. Eligible studies measured both fasting and postprandial FMD following consumption of a meal containing ≥ 30 g fat or ≥ 40% energy from fat. A random-effects model was used to analyse the pooled effect size change from the fasting FMD, presented as mean difference. Moderator variables were analysed by meta-regression. Results One-hundred and twenty articles reporting on 3821 adults were included in the review. High fat meal consumption significantly attenuated FMD at 2 hours (MD: −1.61; 95% CI −2.02 −1.19, p &amp;lt; 0.001), 3 hours (−1.73; −2.30 −1.17, p &amp;lt; 0.001) and 4 hours (−1.54; −1.88 −1.20, p &amp;lt; 0.001), though heterogeneity (I2) was &amp;gt; 90%. Meta-regression revealed that fasting FMD significantly impacted the reported effect size (p &amp;lt; 0.0001) at all postprandial timepoints. Age and BMI were inversely correlated with FMD response at 2 and 4 hours (p &amp;lt; 0.0001). Conclusions Younger, healthy-weight participants exhibited a larger postprandial reduction in FMD compared to older, heavier groups after a high-fat meal. Vulnerable populations could be more likely to exhibit endothelial dysfunction, as evident through lower fasting FMD, together with impaired metabolic flexibility. A single high fat meal adversely impacts endothelial function and the magnitude of the impact on postprandial FMD was influenced by fasting FMD, participant age, and BMI. Funding Sources Monash University

Abstract PS12-15: Pharmacokinetics of H3B-6545 in patients with locally advanced or metastatic estrogen receptor-positive HER2 negative breast cancer (ER+ and HER2- BC)

Abstract RATIONALE: Addition of CDK 4/6 inhibitors to endocrine therapy has become standard for patients (pts) with ER+ and HER2- BC with improvements in overall survival. However, acquired resistance to front-line therapy is inevitable, and response to later-line therapy is poor. H3B-6545 is a selective, orally available, small molecule covalent antagonist of the estrogen receptor (ERα). H3B-6545 binds covalently to a cysteine residue at position 530 of both wild-type and the constitutively active mutant ERα proteins. H3B-6545 demonstrated significant antitumor activity in multiple PDX breast cancer models, including those with mutated ESR1 (the gene encoding ERα). A phase I-II study was conducted to explore the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics, and efficacy of this agent in advanced ER+ and Her2- breast cancer pts (NCT03250676). METHODS: PK samples in phase I were obtained at day 1 and day 15 of cycle 1 (Predose, 0.5, 1, 2, 4, 6, 8, 10, and 24 h post dose) and sparse PK samples were collected in the phase II part of the trial. For pts enrolled in the food effect sub-study of phase II, plasma samples were collected during cycle 1 on day 15 and day 22 (Predose, 0.5, 1, 2, 4, 6, 8, 10, and 24 h post dose). Nonlinear mixed effect model (NONMEM) was applied for development of population PK models to fit H3B-6545 plasma concentration data with NONMEM® version 7.4 software. R was used for data management, visualization and statistical summaries. RESULTS: This phase I-II trial enrolled 47 pts in phase I part and 83 pts in the phase II part at the recommended phase II dose of 450 mg QD as of May 15, 2020. The 1180 plasma concentrations of H3B-6545 from a total of 103 pts at doses of 100-600 mg available as of January 15, 2020 were included in this analysis, with the following characteristics [n or (median, min-max) unit]: race (n=91/5/1/6 for White/Black/Asian/others), age (62.5, 31-81) yrs, body weight (79.5, 49-140) Kg, BMI (26.9, 17.6-45.6) Kg/m2, albumin (40, 29-52) g/dL, ALP (88.5, 39-917) IU/L, ALT (28, 10-193) IU/L, AST (36.5, 13-259) IU/L, bilirubin (8.6, 1.7-25.7) µM and creatinine clearance (112, 49.5-389) mL/min. The median number of prior therapy in the metastatic setting was 3 (range: 1 - 10). Out of 103 patients, 32 pts received treatment with a single high-fat meal to test food effect on PK over a randomized crossover design. H3B-6545 plasma concentrations were best described with a one compartment disposition PK model, plus a combined first- and zero-order parallel absorption and lag time. The estimated apparent clearance (CL/F) and volume of distribution (V/F) were 31 L/h and 422 L, respectively, with a typical terminal half-life of about 10 hours. H3B-6545 was absorbed fast, with a typical tmax of about 4 hours. A moderate to high variability (40-60%) was identified in major PK parameters (CL/F, V/F, bioavailability [F1]). A high-fat meal increased bioavailability by approximately 45% and prolonged tmax, roughly from 4 hours to 6 hours post dose. No significant effect was identified from other covariates: age, body weight, race, albumin, AST, ALP, ALT, bilirubin and creatinine clearance. CONCLUSIONS: H3B-6545 PK profiles in breast cancer patients were well described by a one-compartment disposition model with no significant effect of demographics, liver and renal function. When administered with a high fat meal, H3B-6545 exposure was modestly increased. Citation Format: Oneeb Majid, Jianjun Alan Xiao, Tarek Sahmoud, Sanae Yasuda, Lisa Cantagallo, Erika P Hamilton, Timothy Pluard, Dejan Juric, Antonio Gualberto, Ziad Husseiin. Pharmacokinetics of H3B-6545 in patients with locally advanced or metastatic estrogen receptor-positive HER2 negative breast cancer (ER+ and HER2- BC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-15.

Abstract 16807: The Association Between Dietary Factors and the Distribution of Monocyte Subsets: A Systematic Review

Introduction: Three subsets of monocytes have been identified in humans (i.e. classical, intermediate and non-classical), which have been proposed to differently contribute to the pathogenesis of atherosclerosis, a major cause of cardiovascular disease (CVD). Previous studies implicate a shift in the distribution of monocyte subsets from classical (CM) to intermediate (IM) and non-classical monocytes (NCM) in individuals with cardiometabolic disorders, which is hypothesized to contribute to CVD development. The risk of cardiometabolic disease is strongly associated with dietary habits. Thus, the aim of the current systematic review was to evaluate the association between dietary factors and the distribution of monocyte subsets. Methods: Articles were systematically searched in CINAHL, Cochrane Central Register of Controlled Trials, and PubMed until May 2020. A total of 2496 articles were independently screened by 2 reviewers. Eligible study subjects were adults &gt; 18 years old. Eligible studies were cross-sectional, cohort, within-subject design studies and randomized-controlled trials that examine the effect of dietary factors on monocyte subset distribution. A total of 12 studies were included in this review. Results: A single high fat meal challenge increased the number and percentage of NCM (n=1) and increased the number and percentage of CM (n=1) in healthy subjects. Consuming a high-salt diet for a week increased the number and percentage of IM in healthy subjects, whereas these changes were reversed after switching to a low-salt diet (n=2). EPA+DHA supplementation (4 g/day) for 2 weeks decreased the number and percentage of IM in patients with hypertriglyceridemia (n=2). Lastly, one cross-sectional study showed that the number and percentage of IM was lower in patients with CVD who consumed a high quality diet compared to low quality diet. Conclusions: Dietary factors may influence the distribution of monocyte subsets. However, the role of diet-induced changes in the distribution of monocytes on atherosclerosis risk remains unknown. Additional mechanistic studies are needed to understand the relationship between dietary factors, changes in the distribution of monocyte subsets and atherosclerotic risk.

PREPRANDIALEXERCISE DOES NOT MODIFY HIGH FAT MEAL INDUCED INFLAMMATION IN YOUNG AND OLD ADULTS

An up-regulation of pro-inflammatory cytokines (i.e. IL-6, TNFα, IL-1β, IL-8) and lower anti-inflammatory cytokines (IL-10) are associated with development of cardiovascular disease. While a single high-fat meal (HFM) can transiently increase systemic postprandial inflammation (PPI) in young adults (YA), the effect of a HFM or acute exercise on PPI in older adults (OA) is not clear. PURPOSE: To determine if preprandial exercise attenuates PPI in YA and OA. METHODS: 12 YA (23.3±3.9 years n= 5 M/7 F) and 12 OA (67.7±6 years, n= 8 M/4 F) completed an incremental exercise test to determine VO2peak and then two HFM challenges (HFM alone or acute exercise prior to a HFM (EX+HFM)) in a randomized order. Prior to the HFM (12 kcals/kg body weight: 57% fat, 39% CHO, 4% PRO), participants abstained from strenuous physical activity for 48 hours and adhered to a 12 hour overnight fast. Inflammatory cytokines were measured at baseline, 3, and 6 hours during the HFM. In EX+HFM, participants completed an exercise session on a cycle ergometer 12 hours prior to the HFM at 65% VO2Peak, until caloric expenditure matched 75% of the caloric content of the HFM. RESULTS: There was a significant main effect of time as a quadratic function for IL-6 and IL-8, which decreased by 28% and 8% (respectively) at three hours post-HFM, and then increased near baseline levels at six hours post-HFM (p < 0.05). TNFα, IL-10, and IL-1β exhibited significant decreases over time from baseline to six hours (p < 0.05). Specifically, TNFα decreased by 12% , IL-10 decreased by 7%, and IL-1β decreased by 14% (p < 0.05). TNFα was greater in OA at baseline compared to YA (p = 0.036), however there was no difference post-HFM at either three or six hours (p > 0.05). There was no difference in inflammation between HFM and EX+HFM at any time point for any inflammatory marker (p > 0.05). CONCLUSION: Contrary to our hypotheses, a HFM did not elicit PPI in YA or OA. Additionally, acute exercise did not impact inflammation at any timepoint. Future work should be performed to elucidate the mechanism by which a HFM raises cardiovascular disease risk. Supported by 4-VA grant

Substrate Utilization During High‐Intensity Interval Training as a Novel Index of Metabolic Flexibility

Metabolic flexibility is the ability to appropriately store or utilize substrates and is traditionally assessed during the transition between fasted and feeding. However, exercise is also a robust test of one’s ability to shift between substrates to support metabolic demand. We explored whether an individual’s capacity for substrate shifting during high intensity interval exercise (HIIT) could provide a novel means of assessing metabolic flexibility. The study aim was to determine the relationship between fat oxidation during HIIT and following a single high fat meal (HFM), and the impact of aerobic fitness status and mitochondrial capacity on both HIIT‐ and HFM‐based assessments of metabolic flexibility. Recreationally trained men (n=11) and women (n=7) underwent three sessions. Women were tested during days 1–7 of their menstrual cycle. HIIT sessions were comprised of 4 × 4 min high intensity intervals performed at the power output corresponding to 50% of the difference between the ventilatory threshold and VO2 max. Intervals were separated by 3 min unloaded (0W) active recovery. Respiratory gasses were assessed throughout and for 20 minutes following exercise. Blood glucose, lactate and RPE were collected following each interval and during recovery. HFM sessions included a fasted resting metabolic assessment followed by ingestion of a high fat meal. Blood glucose, resting energy expenditure, fat (FOX) and carbohydrate oxidation (COX) measurements were taken at baseline (T0) and every 30 minutes for four hours during the post prandial period (T1–T8). The high‐fat meal consisted of 0.5 g carbohydrate, 1.3 g fat, and 0.2 g protein per kg FFM. Both testing sessions were conducted after an overnight fast. Participants were split into high aerobic fitness status (HFS; n=9; 23±4 yrs; 22.1±4.7% BF; NIRS 1.8±0.8 sec−1; VO2 max 47.5±4.4 ml/kg/min) or low aerobic fitness status (LFS; n= 10; 22±3 yrs; 25.8±5.0% BF; NIRS 1.16±0.1*sec−1; VO2 max 35.5±3.7*ml/kg/min; *p≤0.05). There was a significant correlation between total g fat oxidized (g/kg) during HIIT and HFM (R2=0.54; p=0.03). Significant correlations were observed between VO2 max vs g fat oxidized (g/kg) during HIIT (R2=0.561; p=0.016) and VO2 max vs total percent of substrate oxidized coming from fat during HIIT (R2=0.585; p=0.011), but not for the HFM. Areas under the FOX and COX (g/kg*total min) curves were greater in HFS than LFS during HIIT (p≤0.05). Differences between groups in Total FOX (g/kg) for HIIT approached significance (p=0.06) with total percent of substrate oxidized during HIIT coming from fat being significantly greater in HFS than LFS (HFS: 11.9±0.04% vs LFS: 6.1±0.02%; p≤0.01). FOX rate (g/kg/min) was significantly increased from baseline to T1 and T6‐T8 across all time points (p&lt;0.05), with no differences between groups at any time point during the HFM. These results indicate a significant relationship between postprandial and exercise metabolic flexibility as indicated by fat oxidation. Despite the observed relationship between HIIT‐ and HFM‐based measures of metabolic flexibility, the HIIT protocol used in the current study may uncover metabolic differences induced by training not captured by the traditional HFM approach.Support or Funding InformationA. Olenick is funded by the Mary Ella Lunday Soule Scholarship.

Deep inspirations attenuate postprandial airway inflammation in college-aged adults with elevated baseline exhaled nitric oxide: A pilot study

Airway inflammation (assessed by exhaled nitric oxide (eNO)) increases after a single high-fat meal (HFM), yet this response may be modified by airway stretch and baseline eNO level.Purpose: The purpose of this study was to investigate whether deep inspirations (DIs) would attenuate airway inflammation post-HFM and whether this is modulated by baseline eNO level.Methods: A total of sixteen healthy college-aged participants completed a randomized cross-over study with 8 lower eNO (14.8 ± 2.0 ppb: 3 M/5F; age: 22.0 ± 2.2 yrs) and 8 higher eNO (29.3 ± 11.6 ppb 5 M/3F; age: 22.5 ± 2.6 yrs) participants. All participants completed a control (CON) condition (no DIs pre-HFM) and DI condition (60 DI’s to total lung capacity immediately pre-HFM) after an overnight fast. The primary outcome was eNO. Participants had 20 minutes to consume the HFM (1 g fat/1 kg body weight) and eNO was performed at 2- and 4- hours post-HFM. To determine whether baseline eNO levels impacted the effect of DI’s, a median split was performed on their baseline eNO level.Results: There was a significant increase in eNO as a main effect of time (p < 0.001). However when analyzing the potential effect of baseline eNO, there was no significant increase in eNO post-HFM in the higher eNO group in the DI condition (p = 0.54). DIs modified the eNO response to a HFM in the group with a higher baseline eNO value.Conclusions: These data display a possible bronchoprotective protect of DIs against postprandial airway inflammation in participants with higher initial eNO level.

Postprandial activation of leukocyte-endothelium interaction by fatty acids in the visceral adipose tissue microcirculation.

High-fat diet (HFD)-induced obesity is associated with accumulation of inflammatory cells predominantly in visceral adipose depots [visceral adipose tissue (VAT)] rather than in subcutaneous ones [subcutaneous adipose tissue (SAT)]. The cellular and molecular mechanisms responsible for this phenotypic difference remain poorly understood. Controversy also exists on the overall impact that adipose tissue inflammation has on metabolic health in diet-induced obesity. The endothelium of the microcirculation regulates both the transport of lipids and the trafficking of leukocytes into organ tissue. We hypothesized that the VAT and SAT microcirculations respond differently to postprandial processing of dietary fat. We also tested whether inhibition of endothelial postprandial responses to high-fat meals (HFMs) preserves metabolic health in chronic obesity. We demonstrate that administration of a single HFM or ad libitum access to a HFD for 24 h quickly induces a transient P-selectin-dependent inflammatory phenotype in the VAT but not the SAT microcirculation of lean wild-type mice. Studies in P-selectin-deficient mice confirmed a mechanistic role for P-selectin in the initiation of leukocyte trafficking, myeloperoxidase accumulation, and acute reduction in adiponectin mRNA expression by HFMs. Despite reduced VAT inflammation in response to HFMs, P-selectin-deficient mice still developed glucose intolerance and insulin resistance when chronically fed an HFD. Our data uncover a novel nutrient-sensing role of the vascular endothelium that instigates postprandial VAT inflammation. They also demonstrate that inhibition of this transient postprandial inflammatory response fails to correct metabolic dysfunction in diet-induced obesity.-Preston, K. J., Rom, I., Vrakas, C., Landesberg, G., Etwebe, Z., Muraoka, S., Autieri, M., Eguchi, S., Scalia, R. Postprandial activation of leukocyte-endothelium interaction by fatty acids in the visceral adipose tissue microcirculation.

Organic beet leaves and stalk juice attenuates HDL-C reduction induced by high-fat meal in dyslipidemic patients: A pilot randomized controlled trial.

Beet leaves and stalks are rich in polyphenols; however, their effect on risk factors for cardiovascular disease in humans, to our knowledge, has not yet been investigated. The aim of this study was to analyze the acute effect of beet leaves and stalk juice, containing different concentrations of polyphenols, on lipemia, glycemic control, nitric oxide concentration, and blood pressure in patients with dyslipidemia after a high-fat meal. In a randomized double-blind, placebo-controlled, crossover pilot study, patients 20 to 59 y of age with dyslipidemia were fed a single high-fat meal supplemented with either a placebo or one of two organic beet leaves and stalk juices rich in polyphenols (32 or 77.5 mg EAG/100 mL) with a 1-wk washout. Thus, each group was composed of 13 patients. Blood samples were obtained at fasting and 30, 60, 120, and 180 min after intervention. Total cholesterol, high-density lipoprotein, triacylglycerols, glucose, insulin, nitrite and nitrate, and blood pressure were assessed at each time period. The high-fat meal increased triacylglycerol levels after 120 (P < 0.001) and 180 min (P < 0.001) and reduced high-density lipoprotein cholesterol after 60 min (P < 0.05). This reduction was attenuated in both groups that received BLS juices after 120 min (P = 0.005). A reduction in diastolic blood pressure within groups that received BLS juice was also observed. There was no significant difference between groups for other biomarkers. The beet leaves and stalk juice attenuated the reduction of high-density lipoprotein cholesterol induced by a high-fat meal.

High-Fat Meal–Induced Changes in Markers of Inflammation and Angiogenesis in Healthy Adults Who Differ by Age and Physical Activity Level

BackgroundInflammation and angiogenesis are key facets of cardiovascular disease pathophysiology. Age and physical activity level can influence fasting systemic inflammation, but the impact of these factors on postprandial inflammation is unknown. In addition, markers of angiogenesis have never been tested in the context of a single high-fat meal (HFM). ObjectiveThe purpose of this study was to investigate the effects of an HFM on markers of inflammation and angiogenesis in individuals of different ages and physical activity levels. MethodsTwenty-two healthy adults—8 younger active (YA) adults (4 men, 4 women; mean ± SD age: 25 ± 5 y), 8 older active (OA) adults (4 men, 4 women; 67 ± 5 y), and 6 older inactive (OI) adults (3 men, 3 women; 68 ± 7 y)—consumed an HFM [63% fat (39% saturated fat, 14% monounsaturated fat, 10% polyunsaturated fat), 34% carbohydrate; 12 kcal/kg body mass; 927 ± 154 kcal]. Fourteen inflammatory and 9 angiogenic markers were measured at baseline and 3 and 6 h postmeal. ResultsSignificant group effects were observed in interleukin (IL)-10 (YA > OA; P = 0.02), IL-23 (YA > OA; P = 0.02), tumor necrosis factor (TNF)-α (OA < OI; P = 0.04), and vascular endothelial growth factor (VEGF)-C (YA < OA; P = 0.001). IL-8, VEGF-A, VEGF-C, and heparin-binding epidermal growth factor–like growth factor significantly increased, whereas granulocyte-macrophage colony-stimulating factor, interferon-γ, IL-1β, IL-5, IL-10, IL-12, IL-13, IL-17A, IL-23, TNF-α, leptin, angiopoietin-2, and follistatin significantly decreased after HFM consumption (P’s < 0.05). Notably, VEGF-A and VEGF-C were significantly higher at 3 h [mean difference: 22.5 pg/mL (VEGF-A); 73.5 pg/mL (VEGF-C)] and 6 h postmeal [mean difference: 26.9 pg/mL (VEGF-A); 81.2 pg/mL (VEGF-C)]. ConclusionsA novel finding of this study was the robust increase in VEGF after an HFM. There were also group differences in several inflammatory markers (IL-10 and IL-23 greater in YA than OA, and TNF-α lower in OA than OI) that suggest a potential influence of age and physical activity level.

A single high-fat meal provokes pathological erythrocyte remodeling and increases myeloperoxidase levels: implications for acute coronary syndrome

High-fat meal (HFM) consumption can produce acute lipemia and trigger myocardial infarction in patients with atherosclerosis, but the mechanisms are poorly understood. Erythrocytes (red blood cells, RBCs) intimately interact with inflammatory cells and blood vessels and play a complex role in regulating vascular function. Chronic high-fat feeding in mice induces pathological RBC remodeling, suggesting a novel link between HFM, RBCs, and vascular dysfunction. However, whether acute HFM can induce RBC remodeling in humans is unknown. Ten healthy individuals were subjected to biochemical testing and assessment of endothelial-dependent flow-mediated dilation (FMD) before and after a single HFM or iso-caloric meal (ICM). Following the HFM, triglyceride, cholesterol, and free fatty acid levels were all significantly increased, in conjunction with impaired post-prandial FMD. Additionally, peripheral blood smears demonstrated microcytes, remodeled RBCs, and fatty monocytes. Increased intracellular ROS and nitration of protein band 3 was detected in RBCs following the HFM. The HFM elevated plasma and RBC-bound myeloperoxidase (MPO), which was associated with impaired FMD and oxidation of HDL. Monocytic cells exposed to lipid in vitro released MPO, while porcine coronary arteries exposed to fatty acids ex vivo took up MPO. We demonstrate in humans that a single HFM induces pathological RBC remodeling and concurrently elevates MPO, which can potentially enter the blood vessel wall to trigger oxidative stress and destabilize vulnerable plaques. These novel findings may have implications for the short-term risk of HFM consumption and alimentary lipemia in patients with atherosclerosis.A single high fat meal can induce pathological red blood cell (RBC) remodeling and oxidative stress, in conjunction with elevations in plasma, RBC-bound myeloperoxidase (MPO) and MPO-mediated high-density lipoprotein oxidation. These findings demonstrate that consumption of heavy meals enriched in fat may promote destabilization of vulnerable plaques leading to acute myocardial infarction.

Issue Highlight - July 2018.

Issue Highlight - July 2018.

A single high-fat meal alters human soluble RAGE profiles and PBMC RAGE expression with no effect of prior aerobic exercise.

A high‐fat diet can induce inflammation and metabolic diseases such as diabetes and atherosclerosis. The receptor for advanced glycation endproducts (RAGE) plays a critical role in metabolic disease pathophysiology and the soluble form of the receptor (sRAGE) can mitigate these effects. However, little is known about RAGE in the postprandial condition and the effect of exercise in this context. Thus, we aimed to determine the effects of a single high‐fat meal (HFM) with and without prior exercise on peripheral blood mononuclear cell (PBMC) RAGE biology. Healthy males (n = 12) consumed a HFM on two occasions, one without prior exercise and one 16–18 hours following acute aerobic exercise. Total soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) were determined via ELISA and cleaved RAGE (cRAGE) was calculated as the difference between the two. Isolated PBMCs were analyzed for RAGE, ADAM10, TLR4, and MyD88 protein expression and ADAM10 activity. The HFM significantly (P < 0.01) attenuated sRAGE, esRAGE, and cRAGE by 9.7%, 6.9%, and 10.5%, respectively. Whereas, the HFM increased PBMC RAGE protein expression by 10.3% (P < 0.01), there was no meal effect on PBMC TLR4, MYD88, or ADAM10 protein expression, nor ADAM10 activity. There was also no exercise effect on any experimental outcomes. These findings suggest that PBMC RAGE and soluble RAGE may be important in the postprandial response to a HFM, and that prior aerobic exercise does not alter these processes in young healthy adult males. The mechanisms by which a HFM induces RAGE expression and reduces circulating soluble RAGE isoforms requires further study.