High-fat Meal Challenge Research Articles

Metabolic Flexibility in Response to a High-Fat Meal Challenge Is Not a Universal Indicator of Overall Metabolic Health

Metabolic Flexibility in Response to a High-Fat Meal Challenge Is Not a Universal Indicator of Overall Metabolic Health

Are postprandial glucose responses sufficiently person-specific to use in personalized dietary advice? Design of the RepEAT study: a fully controlled dietary intervention to determine the variation in glucose responses.

An elevated postprandial glucose response is associated with an increased risk of cardiometabolic diseases. Existing research suggests large heterogeneity in the postprandial glucose responses to identical meals and food products between individuals, but the effect of other consumed meals during the day and the order of meals during the day on the heterogeneity in postprandial glucose responses still needs to be investigated. In addition, the robustness of the glucose responses to meals or foods is still unknown. The overall aim of the project is to assess whether the glucose response to a meal is sufficiently person-specific to use in personalized dietary advice. We aim to answer the question: "How replicable are glucose responses to meals within individuals and how consistent is the variation in glucose responses between individuals?" The question will be assessed under standardized conditions of a 9-week fully controlled dietary intervention in which all meals are the same between individuals and consumed in a fixed order at a fixed time. 63 apparently healthy men and women with a BMI of 25-40 kg/m2 and aged 45-75 years were enrolled in the RepEAT study (NCT05456815), of whom 53 participants completed the study. The RepEAT study comprised a fully controlled dietary intervention of nine weeks, consisting of three repetitive periods of three weeks. Within each three-week period, a variety of meals and food products were offered during breakfast, lunch, dinner and in between meal snacks. Throughout the dietary intervention, glucose was continuously monitored using Freestyle Libre Pro IQ monitors. Physical activity was monitored using the ActiGraph and ActivPAL. To measure the association between glucose responses and an individual's phenotype, various measurements were performed before the start of the dietary intervention including an oral glucose tolerance test, a high-fat mixed meal challenge, assessment of body fat distribution including liver fat (MRI/MRS), and cardiometabolic markers. The repetitive and fully controlled nature of the dietary study allows detailed assessment of the replicability of the glucose responses to meals and food products within individuals. Furthermore, the consistency of the variation between individuals independent of insulin resistance will be determined.

Plasma Metabolome Analysis Suggests That L-Arginine Supplementation Affects Microbial Activity Resulting in a Decrease in Trimethylamine N-oxide—A Randomized Controlled Trial in Healthy Overweight Adults with Cardiometabolic Risk Factors

BackgroundThe effects of supplementation with L-arginine (L-arg), the precursor of nitric oxide (NO), on vascular and cardiometabolic health have largely been explored. Whether other mechanisms of the action of L-arg exist remains unknown, as arginine metabolism is complicated. ObjectiveWe aimed to characterize the effect of low dose L-arg supplementation on overall human metabolism both in a fasting state and in response to an allostatic stress. MethodsIn a randomized, double-blind, crossover study, 32 healthy overweight adults (mean age 45 y) with cardiometabolic risk (fasting plasma triglycerides >150 mg/dL; waist circumference >94 cm [male] or >80 cm [female]) were treated with 1.5 g sustained-release L-arg 3 times/d (4.5 g/d) or placebo for 4 wk. On the last day of treatment, volunteers consumed a high-fat meal challenge (900 kcal, 80% as fat, 13% as carbohydrate, and 7% as protein). Plasma was collected at fasting, 2, 4, and 6 h after the challenge, and the metabolome was analyzed by high-resolution liquid chromatography–mass spectrometry. Metabolic profiles were analyzed using linear mixed models–principal component analysis. ResultsThe challenge meal explained most of the changes in the metabolome. The overall effect of L-arg supplementation significantly explained 0.5% of the total variance, irrespective of the response to the challenge meal (P < 0.05). Among the metabolites that explain most of the L-arg effect, we found many amino acids, including branched-chain amino acids, that were decreased by L-arg supplementation. L-arg also decreased trimethylamine N-oxide (TMAO). Other changes suggest that L-arg increased methyl demand. ConclusionsAnalysis of the effect of 4 wk of L-arg supplementation on the metabolome reveals important effects on methyl balance and gut microbiota activity, such as a decrease in TMAO. Further studies are needed to investigate those mechanisms and the implications of these changes for long-term health.This trial was registered at clinicaltrials.gov as NCT02354794.

Hunger and satiety responses to diets enriched with cottonseed oil vs. olive oil

Studies suggest that the type of dietary fat consumed habitually may modulate appetite and further influence weight management. The purpose of this study was to evaluate the impact of an 8-week diet intervention enriched with either cottonseed oil (CSO; polyunsaturated fat-rich) or olive oil (OO; monounsaturated fat-rich) on appetite responses in adults with high cholesterol. This was a parallel design, randomized partial outpatient feeding trial designed to provide approximately 60% of participants daily energy needs with ∼30% of energy needs as CSO (n = 21, BMI 27.3 ± 0.92 kg/m2, age 53 ± 2y) or OO (n = 21, BMI 27.6 ± 1.20 kg/m2, age 54 ± 2y). A high saturated fat meal challenge was completed at pre- and post-intervention visits with 5 h postprandial blood draws and visual analog scales (VAS) for cholecystokinin (CCK), peptide YY (PYY), ghrelin, and subjective appetite, respectively. Participants also completed VAS questionnaires hourly and recorded dietary intake after leaving the lab for the remainder of the day. There was a greater increase in fasting CCK (CSO: 0.54 ± 0.03 to 0.56 ± 0.04; OO: 0.63 ± 0.07 to 0.60 ± 0.06 ng/ml p = 0.05), a greater suppression of postprandial ghrelin (p < 0.01), and a greater increase in postprandial VAS fullness (p = 0.04) in CSO compared to OO. Additionally, there was a greater decrease in self-reported energy intake in CSO compared to OO (CSO: 2464 ± 123 to 2115 ± 123; OO: 2263 ± 147 to 2,434 ± 184 kcal/d p = 0.02). Only postprandial VAS prospective consumption showed greater suppression (p = 0.03) in OO vs. CSO. Altogether, these data show that CSO has a greater effect on appetite suppression than OO diet enrichment and may be beneficial for weight maintenance, especially in a population at-risk for chronic disease. Registered at clinicaltrials.gov: NCT04397055

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.

New evidence for dietary fatty acids in the neutrophil traffic between the bone marrow and the peripheral blood

Chronic administration of a high-fat diet in mice has been established to influence the generation and trafficking of immune cells such as neutrophils in the bone marrow, the dysregulation of which may contribute to a wide range of diseases. However, no studies have tested the hypothesis that a short-term, high-fat diet could early modulate the neutrophil release from bone marrow at fasting and at postprandial in response to a high-fat meal challenge, and that the predominant type of fatty acids in dietary fats could play a role in both context conditions. Based on these premises, we aimed to establish the effects of different fats [butter, enriched in saturated fatty acids (SFAs), olive oil, enriched in monounsaturated fatty acids (MUFAs), and olive oil supplemented with eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids] on neutrophil navigation from bone marrow to blood in mice. The analysis of cellular models for mechanistic understanding and of postprandial blood samples from healthy volunteers for translational purposes was assessed. The results revealed a powerful effect of dietary SFAs in promotion the neutrophil traffic from bone marrow to blood via the CXCL2-CXCR2 axis. Dietary SFAs, but not MUFAs or EPA and DHA, were also associated with increased neutrophil apoptosis and bone marrow inflammation. Similar dietary fatty-acid-induced postprandial neutrophilia was observed in otherwise healthy humans. Therefore, dietary MUFAs might preserve bone marrow health and proper migration of bone marrow neutrophils early in the course of high-fat diets even after the intake of high-fat meals.

SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults

BackgroundThe effect of genetic polymorphisms on fasting blood lipid levels have been widely studied but the effects of these within the context of a high-fat meal challenge remain less characterized. The current study aimed to investigate the association of SNPs in lipoprotein-related genes with blood lipid profiles in healthy adults in the U.S.MethodsSubjects (n = 393) between 18–66 years of age with BMIs ranging from 18.5–45 kg/m2 were enrolled the cross-sectional Nutritional Phenotyping Study. Among them, 349 subjects (men: 48%; women: 52%) gave consent for genotyping. SNPs in APOA5, APOB, APOC3, APOE, and LDLR were assessed. The association between lipid markers and genotypes was tested separately for each SNP with analysis of variance (ANOVA), adjusted for sex, age, and BMI. We also examined two-factor interactions between SNPs and sex, age, or BMI.ResultsWomen carrying the C allele of rs3135506 in APOA5 or men carrying the C allele of rs429358 in APOE had reduced HDL-cholesterol levels during fasting and postprandially. The C allele in APOE was also correlated to increased LDL-C levels. The TT genotype of rs2854116 in APOC3 was associated with elevated total cholesterol. Additive effect of the risk alleles of APOA5 and APOE or APOC3 and APOE was detected. Nevertheless, the tested SNPs had little impact on the postprandial triglyceride responses to the high-fat challenge meal. We found no significant effects of SNPs in APOB (rs1042034) or LDLR (rs2228671) on triglycerides, cholesterol, or free fatty acid levels.ConclusionsIn healthy adults, fasting and postprandial cholesterol levels are strongly correlated with the tested APOA5, APOE, and APOC3 genotypes. Sex contributes to the genetic impact of the tested SNPs on lipid profiles.Trial registrationClinicalTrials.gov, NCT02367287. Registered February 20, 2015, https://clinicaltrials.gov/ct2/show/NCT02367287.

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.

Impact Of Moderate-to-vigorous Physical Activity And Visceral Adiposity On Postprandial Triglycerides In Metabolically At-risk Adults

Postprandial lipemia occurs early in chronic disease progression. The degree of postprandial triglyceride (ppTG) is influenced by physiological and lifestyle factors such as diet, central obesity, and physical activity (PA). However, it is unclear how habitual dietary factors and PA impact ppTG in healthy adults with high central adiposity. PURPOSE: To examine the impact of habitual moderate-to-vigorous PA (MVPA), saturated fat (SF) in the habitual diet, and central adiposity on ppTG in metabolically at-risk adults. METHODS: Non-diabetic adults (n = 21) with a high waist circumference (> 35” women, >40” men) completed a high-fat meal challenge (50 g FAT, 54 g CHO, 12 g PRO), with blood collected at fasting and hourly after meal ingestion for 5 h. TG (mmol/L) was determined by lipid panels and summarized as iAUC and the change from fasting (TGmax). Habitual dietary data was collected through the online DHQ-III, with SF percentage (SF / total fat) used for analysis. Visceral adipose tissue (VAT) was determined through bioelectrical impedance analysis. Participants wore an accelerometer for 7 days (>10 h/day) and average number of MVPA bouts/day (≥ 2690 counts/min) was derived. Separate linear models for TG iAUC and TG magnitude were used to test the impact of an interaction between average MVPA bouts and VAT, accounting for habitual dietary SF. RESULTS: MVPA, VAT, and habitual dietary SF explain ~36% of variation in TG iAUC and TGmax. Average MVPA bouts and VAT jointly impacted TG iAUC (p < 0.01), with a ppTG-lowering effect observed with lower VAT and more frequent MVPA bouts and a pronounced ppTG-raising effect observed with greater VAT with frequent MVPA bouts (β = 1.1). Habitual SF did not predict TG iAUC (p = 0.68). Likewise, average MVPA bouts and VAT impacted TGmax (p = 0.03), with a TG-raising effect observed with greater VAT despite more MVPA bouts (β = 0.31). Interestingly, an inverse relationship was observed between habitual SF intake and TGmax (β = - 0.04, p = 0.02). CONCLUSION: Frequent MVPA promotes lower ppTG, a benefit that is reversed with increased VAT. These findings suggest that increased VAT promotes ppTG even with regular MVPA, stressing the importance of strategies to decrease VAT in improving regulation of postprandial lipemia in at-risk adults. Supported by USDA-ARS Pulse Crop Health Initiative 58-3060-9-040.

The Role of Fitness Status and Sex on Metabolic Flexibility during a Bout of High-Intensity Interval Exercise and a High-Fat Meal Challenge

We explored whether High-Intensity Interval Exercise (HIIE) could provide a novel method to test metabolic flexibility during exercise. We also aimed to assess substrate oxidation during HIIE and in response to a high-fat meal to determine if these assessments of metabolic flexibility are influenced by fitness and sex.

TMAO Response to a High-Fat High-Sugar Meal Challenge in Generally Healthy United States Adults

ObjectivesTrimethylamine n-oxide (TMAO) is linked to the gut microbiome's metabolism of choline, carnitine, and betaine and is associated with adverse cardiovascular health. In a secondary analysis, we assessed the plasma TMAO response to a high-fat high-sugar meal challenge devoid of choline, carnitine, or betaine in metabolically healthy male (n = 48) and female (n = 49) participants residing near Davis, California, USA.MethodsThe standardized meal challenge was a 3000-gram shake containing 60% kilocalories from fat (shortening and palm oil), 25% kilocalories from carbohydrate (granulated white sugar), and 15% kilocalories from protein (pasteurized egg white). The shake contained limited amounts of direct TMAO-precursors including 2.9 mg of choline and 0.76 mg of betaine. Blood samples were collected at fasting and 0.5, 3, and 6 hours after consuming the meal challenge. TMAO was measured by liquid chromatography-high resolution mass spectrometry using the MxP Quant 500 kit (Biocrates, Innsbruck, Austria). Differences in TMAO concentration by time were assessed by ANOVA and values are means ± standard deviation.ResultsTMAO response demonstrated a post-prandial rise in concentration that peaked at 3 hours and returned to fasting levels by 6 hours. Mean TMAO levels at fasting, 0.5, 3, and 6 hours were 5.27 ± 3.43 μM, 6.09 ± 6.01 μM, 6.87 ± 8.11 μM, 4.76 ± 4.00 μM, respectively. Significant differences were observed between fasting and 3 hours (P = 0.039), and 3 and 6 hours (P = 0.011).ConclusionsPlasma TMAO concentration was affected by a high-fat high-sugar meal challenge despite providing limited amounts of direct TMAO-precursors. The circadian rhythm of the gut microbiome or the host, or the gut microbiome's utilization of phosphatidylcholine from biological sources may contribute to these results. Understanding the regulation of TMAO and its relationship to meals is critical to identifying its role in the etiology of diabetes and cardiovascular disease.Funding SourcesThis work was funded in part by the USDA-Agricultural Research Service (2032–51,530-025–00D) and the National Institute of Health (RO1HL148110).

Postprandial Glycemic and Lipidemic Effects of Anthocyanins in Food Matrices of Differing Macronutrient Compositions

ObjectivesWhile a diet rich in anthocyanins is encouraged as a strategy against metabolic disorders, the postprandial benefits of anthocyanin in commonly consumed meals of varying macronutrient compositions and food matrices are unknown. Using a well-characterized source of anthocyanin from black rice, we investigate the postprandial effects of black rice anthocyanin extract (BRAE) enrichment on the glycemic and lipidemic responses to a high-carbohydrate (HC) food and a high-fat (HF) meal challenge. MethodsIn two separate human trials of 24 participants each, the postprandial glycemic and lipidemic responses to HC BRAE-enriched bun, or HF BRAE-enriched burger meal were assessed. Clinically relevant blood biochemical markers for glucose, insulin, and lipids were measured. In addition, we simulated in-vitro digestion models to understand the mechanistic effects of anthocyanins on starch digestibility and lipase activity in the food matrices. ResultsIn-vivo, BRAE enrichment presented a 27-point glycemic index reduction of the HC bun. Significant improvements in postprandial HDL cholesterol and lipoproteins were observed in response to the HF BRAE-burger, while postprandial triglyceride levels did not differ. In-vitro, BRAE enrichment significantly reduced starch digestibility for the BRAE-bun, but not the burger. However, pancreatic lipase activity was greatly reduced in the burger with BRAE enrichment. Altogether, our work has demonstrated improvements in glycemic control with BRAE enrichment, via mechanisms inhibiting starch digestibility. BRAE enrichment also improved lipidemic control, in which our work suggests a modulatory effect of anthocyanins on lipoproteins in-vivo. ConclusionsFindings from this study suggest potential in using BRAE in food enrichment, for improved glycemic and lipidemic control via GI-lowering and lipoprotein modulatory effects. However, the benefits reaped from anthocyanin intake is food matrix-specific, and results should be adapted according to its food application. Funding SourcesThis research is supported by National University Health System and National University of Singapore under the Health Innovation Programme grants C-172–000-064–091 and N-172–000-120–001. Additional funding was provided by the Ministry of Education, via the Academic Research Fund Tier 1 grant R-143–000-A85-114.

Determinants of the postprandial triglyceride response to a high-fat meal in healthy overweight and obese adults

BackgroundDyslipidemia is a feature of impaired metabolic health in conjunction with impaired glucose metabolism and central obesity. However, the contribution of factors to postprandial lipemia in healthy but metabolically at-risk adults is not well understood. We investigated the collective contribution of several physiologic and lifestyle factors to postprandial triglyceride (TG) response to a high-fat meal in healthy, overweight and obese adults.MethodsOverweight and obese adults (n = 35) underwent a high-fat meal challenge with blood sampled at fasting and hourly in the 4-hour postprandial period after a breakfast containing 50 g fat. Incremental area under the curve (iAUC) and postprandial magnitude for TG were calculated and data analyzed using a linear model with physiologic and lifestyle characteristics as explanatory variables. Model reduction was used to assess which explanatory variables contributed most to the postprandial TG response.ResultsTG responses to a high-fat meal were variable between individuals, with approximately 57 % of participants exceeded the nonfasting threshold for hypertriglyceridemia. Visceral adiposity was the strongest predictor of TG iAUC (β = 0.53, p = 0.01), followed by aerobic exercise frequency (β = 0.31, p = 0.05), insulin resistance based on HOMA-IR (β = 0.30, p = 0.04), and relative exercise intensity at which substrate utilization crossover occurred (β = 0.05, p = 0.04). For postprandial TG magnitude, visceral adiposity was a strong predictor (β = 0.43, p < 0.001) followed by aerobic exercise frequency (β = 0.23, p = 0.01), and exercise intensity for substrate utilization crossover (β = 0.53, p = 0.01).ConclusionsPostprandial TG responses to a high-fat meal was partially explained by several physiologic and lifestyle characteristics, including visceral adiposity, insulin resistance, aerobic exercise frequency, and relative substrate utilization crossover during exercise.Trial RegistrationClinicalTrials.gov, NCT04128839, Registered 16 October 2019 – Retrospectively registered.

Temporal metabolic response yields a dynamic biosignature of inflammation

SummaryChronic low-grade inflammation is a subclinical condition directly and indirectly linked to the development of a wide range of diseases responsible for the vast majority of morbidity. To examine mechanisms coupled to chronic disease, a group of overweight and obese human subjects without known inflammatory diseases participated in a high-fat meal challenge as an acute inflammation stimulus. Analysis of serum metabolites grouped by baseline cytokine levels revealed that single samples had little power in differentiating groups. However, an analysis that incorporated temporal response separated inflammatory response phenotypes and allowed us to create a metabolic signature of inflammation which revealed metabolic components that are crucial to a cytokine-mediated inflammation response. The use of temporal response, rather than a single time point, improved metabolomic prediction of high postprandial inflammation responses and led to the development of a dynamic biosignature as a potential tool for stratifying risk to a wide range of diseases.

High-fat meal increases peripheral blood mononuclear cell pro-inflammatory cytokine expression in African-American women.

African-American (AA) women have elevated predominance of inflammatory diseases concurrent with local inflammation resulting in compromised metabolic function. The purpose of the study was 2-fold: 1) to examine the gene and protein expression of pro- and anti-inflammatory cytokine secretion by peripheral blood mononuclear cells (PBMC) obtained from AA and Caucasian-American (CA) women in response to an acute high-fat meal; and 2) to explore the influence of race (AA vs. CA) on PBMC reactivity. Ten AA and 11 CA women consumed a high-fat meal with baseline and 4h postprandial venous blood draws. PBMCs were incubated for 3 h then messenger RNA expression and supernatant protein concentration was used to examine inflammatory profiles. All women had a postprandial increase in interleukin (IL)-8 gene expression, IL-8 protein concentration, and tumor necrosis factor alpha (TNF-α) protein concentration (P< 0.05). AA women had a postprandial increase in IL-6, IL-8, and TNF-α protein concentration (P< 0.05). AA women had higher postprandial IL-1β protein concentration and IL-8 gene expression compared with CA women (P< 0.05). Our data uncovers the specific impact of race and time on pro-inflammatory PBMC (IL-1β, IL-6, IL-8, and TNF-α) expression profiles in response to an acute high-fat meal challenge. Novelty: African Americans have higher predominance of inflammatory disease. We explored the potential race impact on peripheral blood mononuclear cell reactivity in response to a meal. A pro-inflammatory response to an acute high-fat meal with race impact was observed possibly contributing to health disparities impacting African-American women.

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.

Liraglutide treatment in overweight and obese patients with type 1 diabetes: A 26-week randomized controlled trial; mechanisms of weight loss.

To investigate the effects of liraglutide treatment on glycaemic control and adipose tissue metabolism in overweight and obese people with type 1 diabetes (T1DM). A total of 84 adult overweight and obese patients with T1DM, with no detectable C-peptide, were randomized (1:1) to either placebo or 1.8 mg/d liraglutide for 6 months. Blood samples were collected at 0, 12 and 26 weeks. Subcutaneous adipose tissue biopsies, a high-calorie high-fat meal challenge test, continuous glucose monitoring, dual-energy X-ray absorptiometry and MRI were performed before and at the end of treatment. In all, 37 and 27 patients who received liraglutide and placebo, respectively, completed the study. Glycated haemoglobin fell by 0.41 ± 0.18% (4.5±1.4 mmol/mol) from baseline after liraglutide treatment (P = 0.001), and by 0.29 ± 0.19% (3.1±2.0 mmol/mol) compared to placebo (P = 0.1). There was no increase in hypoglycaemia, while the time spent in normal glycaemia increased (P = 0.015) and time spent in hyperglycaemia decreased (P = 0.019). Body weight fell significantly in the liraglutide group, mostly in the form of fat mass loss (including visceral fat), with no change in lean mass. Systolic blood pressure (SBP) also fell after liraglutide treatment. Liraglutide also caused a significant increase in the expression of adipose tissue triglyceride lipase, carnitine palmitoyl transferase-1, peroxisome proliferator-activated receptor (PPAR)α, PPARδ, uncoupling protein-2 and type 2 iodothyronine deiodinase in the adipose tissue. Liraglutide improves glycaemia, reduces adiposity and SBP. Liraglutide also stimulates mechanisms involved with an increase in lipid oxidation and thermogenesis, while conserving lean body mass.

Temporal Metabolic Response Yields a Dynamic Biosignature of Inflammation

Chronic low-grade inflammation is a subclinical condition directly and indirectly linked to the development of a wide range of highly prevalent diseases responsible for the vast majority of morbidity. To examine mechanisms coupled to chronic disease, a group of overweight and obese human subjects without known inflammatory diseases were selected. Study participants underwent a high-fat meal challenge as an inflammation stimulus. Fasting and post-prandial serum samples were analyzed for pro-inflammatory cytokines and metabolites. Analysis of serum metabolites grouped by baseline cytokine levels revealed that single samples had little power in differentiating the groups. However, an analysis that incorporated temporal response separated high and low inflammatory response phenotypes and allowed us to create a metabolic signature of inflammation. The use of temporal response rather than absolute concentrations dramatically improved clinical diagnostics in this study and suggests that dynamic biosignatures may be a powerful tool for stratifying risk to a wide range of diseases.

Serum endotoxin, gut permeability and skeletal muscle metabolic adaptations following a short term high fat diet in humans

BackgroundOur previous work demonstrated that a short-term high fat diet (HFD) increased fasting serum endotoxin, altered postprandial excursions of serum endotoxin, and led to metabolic and transcriptional responses in skeletal muscle in young, healthy male humans. PurposeThe purpose of the present study was to determine if a short-term high fat diet: 1) increases intestinal permeability and, in turn, fasting endotoxin concentrations and 2) decreases postprandial skeletal muscle fat oxidation. MethodsThirteen normal weight young adult males (BMI 23.1 ± 0.8 kg/m2, age 22.2 ± 0.4 years) were fed a control diet (55% carbohydrate, 30% fat, 9% of which was saturated, 15% protein) for two weeks, followed by 5 days of an isocaloric HFD (30% carbohydrate, 55% fat, 25% of which was saturated, 15% protein, isocaloric to the control diet). Intestinal permeability (via four sugar probe test) was assessed in the fasting state. Both before and after the HFD, a high fat meal challenge (HFM, 820 kcal, 25% carbohydrate, 63% fat, 26% of which was saturated, and 12% protein) was administered. After an overnight fast, blood samples were collected before and every hour for 4 h after the HFM to assess endotoxin, and other serum blood measures. Muscle biopsies were obtained from the vastus lateralis before and 4 h after the HFM in order to assess substrate oxidation (glucose, fatty acid and pyruvate) using radiolabeled techniques. Insulin sensitivity was assessed via intravenous glucose tolerance test. Intestinal permeability, blood samples and muscle biopsies were assessed in the same manner before and following the HFD. Main findingsIntestinal permeability was not affected by HFD (p > 0.05), but fasting endotoxin increased two fold following the HFD (p = 0.04). Glucose oxidation and fatty acid oxidation in skeletal muscle homogenates significantly increased after the HFM before the HFD (+97%, and +106% respectively) but declined after the HFM following 5 days of the HFD (−24% and +16% respectively). Fatty acid suppressibility of pyruvate oxidation increased significantly after the HFM (+32%) but this physiological effect was abolished following 5 days of the HFD (+7%). Insulin sensitivity did not change following the HFD. ConclusionThese findings demonstrate that in healthy young men, consuming an isocaloric HFD for 5 days increases fasting endotoxin, independent of changes in gut permeability. These changes in endotoxin are accompanied by a broad effect on skeletal muscle substrate metabolism including increases in postprandial fat oxidation. Importantly, the latter occurs independent of changes in body weight and whole-body insulin sensitivity.

Effects of a High Fat Meal Challenge with Different Doses of Spice Blend on Postprandial Fatty Acid Suppression (P08-094-19)

ObjectivesHigh fat meals can increase inflammation and plasma triglycerides. Poor suppression of postprandial adipocyte lipolysis results in higher levels of non-esterified fatty acids (NEFA) in insulin resistant subjects. This impaired suppression of NEFA may exacerbate hypertriglyceridemia following a high fat meal by increasing available fatty acids. We have shown myristic acid (MA) and stearic acid (SA) are less suppressed than other fatty acids 1 hour following a glucose challenge, and this pattern may indicate optimal adipocyte insulin sensitivity. It is unknown if the same pattern occurs in other contexts, such as high fat meal. MethodsPlasma samples were collected from 12 obese male subjects at baseline and 4 time points following a high fat meal (1076 kcal, 39% kcal from saturated fat) on three visits. Meals contained either 0, 2, or 6 grams of a spice blend. Plasma was analyzed by GC-MS to measure multiple fatty acids, including MA, SA, palmitic acid (PA), oleic acid (OA), and linoleic acid (LA). ResultsAt 1 hour following the high fat meal, MA and SA were less suppressed than OA, PA, and LA (P < 0.0001). Total NEFA concentrations were most suppressed (61%; CI: 46%, 76%) at 2 hours following the meal and remained suppressed until 4 hours. PA (59%, P < 0.0001), SA (43%, P < 0.001), OA (68%, P < 0.0001), and LA (71%, P < 0.0001) also achieved maximal suppression at 2 hours and remained suppressed. MA was suppressed (34%, P = 0.0002) at 1 hour, then returned to baseline. Compared to baseline, all saturated fatty acids increased as % of total NEFA at 2 hours (MA: 0 hr, 1.8%, 2 hr, 3.7%, P < 0.0001; PA: 0 hr, 24%, 2 hr, 26%, P = 0.009; SA: 0 hr, 8%, 2 hr, 12%, P < 0.0001), while the unsaturated fatty acids decreased (OA: 0 hr, 33%, 2 hr, 25%, P < 0.0001; LA: 0 hr, 24%, 2 hr, 19%, P < 0.0001). There was no significant effect of spice. ConclusionsNEFA was most suppressed at 2 hours following a high fat meal challenge, but MA and SA were suppressed less than all other fatty acids. Saturated fatty acids increased as a % of total NEFA following the meal challenge, while unsaturated fatty acids decreased. These data support our previous findings that MA and SA are less suppressed by insulin than other fatty acids. Funding SourcesMcCormick Science Institute; Penn State Department of Nutritional Sciences; National Center for Advancing Translational Sciences, NIH, (UL1 TR002014).