Fat Meal Research Articles

A Review of Cholesterol's Dual Impact: Human Health and Environmental Consequences

Abstract Indiscriminate consumption of fatty foods especially those with higher percentage of saturated fatty acids in and around the world is likely to be in excesses in few years to come. This is particularly so owing to man detrimental eating habits. And this portends a potential risk for coronary heart diseases among unsuspecting consumers. Although man has the enzymatic capacity to convert excess fatty acids to harmless substrates within the body system, but there occur serious pressure on such functions when they are in excesses of the normal daily body requirement. The impact of heavily rich fat meals to the large supply of total fats and its saturated fatty acids derivatives in the human system has been largely traced to dietary intake of lipid rich diets. Their consequential effect over time can damage arteries, contribute to heart disease, and even stroke among unsuspecting consumers. Incidentally this has been traced to cholesterol (lipoprotein), a waxy substance that the body requires to perform certain critical functions including digestion, circulation, and growth and even the nervous system regulation. There are two distinct forms are known these lipoproteins; high density and Low density lipoproteins. Even though both are essential, the excessive intake of the low-density lipoprotein (LDL) is dangerous could trigger certain cardiovascular diseases and even death due to its excessive accumulation in the body. In spite of these foregoing however, they plays very critical roles in the life of virtually all living organisms including man. Therefore it harps on the study for a comprehensive review about the concept and dispels the misinformation about the significance and implication of effects of both saturated and unsaturated fatty acids as probable precursor for certain cardiovascular ailments. Little wonder that some conscious individuals are cautious in choosing their meals owing to this trepidation. It therefore becomes imperative to undertake a study on related works with a view to giving suitable medical information to arm individuals with reliable data towards the trend. Keywords – Food, diets, fats, cardiovascular diseases, heart attack.

Enterocyte-specific FATP4 deficiency elevates blood lipids via a shift from polar to neutral lipids in distal intestine.

Fatty acid transport protein (FATP)4 was thought to mediate intestinal lipid absorption, which was disputed by a study using keratinocyte-Fatp4-rescued Fatp4-/- mice. These knockouts when fed with a Western diet showed elevated intestinal triglyceride (TG) and fatty acid levels. To investigate a possible role of FATP4 on intestinal lipid processing, ent-Fatp4 (KO) mice were generated by Villin-Cre-specific inactivation of the Fatp4 gene. We aimed to measure circulating and intestinal lipids in control and KO mice after acute or chronic fat intake or during aging. Remarkably, ent-Fatp4 mice displayed an approximately 30% decrease in ileal behenic, lignoceric, and nervonic acids, ceramides containing these FA, as well as, ileal sphingomyelin, phosphatidylcholine, and phosphatidylinositol levels. Such decreases were concomitant with an increase in jejunal cholesterol ester. After a 2-wk recovery from high lipid overload by tyloxapol and oral-lipid treatment, ent-Fatp4 mice showed an increase in plasma TG and chylomicrons. Upon overnight fasting followed by an oral fat meal, ent-Fatp4 mice showed an increase in plasma TG-rich lipoproteins and the particle number of chylomicrons and very low-density lipoproteins. During aging or after feeding with a high-fat high-cholesterol (HFHC) diet, ent-Fatp4 mice showed an increase in plasma TG, fatty acids, glycerol, and lipoproteins as well as intestinal lipids. HFHC-fed KO mice displayed an increase in body weight, the number of lipid droplets with larger sizes in the ileum, concomitant with a decrease in ileal ceramides and phosphatidylcholine. Thus, enterocyte FATP4 deficiency led to a metabolic shift from polar to neutral lipids in distal intestine rendering an increase in plasma lipids and lipoproteins.NEW & NOTEWORTHY Enterocyte-specific Fatp4 deficiency in mice increased intestinal lipid absorption with elevation of blood lipids during fasting and aging, as well as after an acute oral fat-loading or chronic HFHC feeding. Lipidomics revealed that knockout mice displayed a shift from very long-chain to long-chain fatty acids, and from polar to neutral lipids, predominantly in the ileum. Thus, FATP4 may have a physiological function in the control of blood lipids via metabolic shifts in distal intestine.

Role of gastrointestinal appetite hormones in the success of body mass loss during interventions based on exercise combined with restricted energy intake diets with different fat and carbohydrate content

Restriction of energy intake is an effective strategy for achieving body mass loss(1). However, it leads to gastrointestinal appetite hormonal changes, which are expected to enhance hunger, reduce satiety, and possibly impair the ability to comply with prescribed intervention(2). Exercise interventions, on the other hand, did not modify gastrointestinal appetite hormones(3) and there is some evidence that postprandial appetite hormone responses after a low carbohydrate-high fat meal (LCHF) are more favorable than after high carbohydrate-low fat meal (HCLF) meal (4). This study investigated how energy-restricted diets based on LCHF and HCLF meals and combined with exercise affect body weight, and gastrointestinal appetite hormones and explored the relationship between body mass changes and changes in gastrointestinal appetite hormones.Twenty-seven overweight and obese females (age: 35 ± 9.35 years, BMI: 31.64 ± 5.08 kg/m2) completed a randomized parallel design study and underwent a 4-week intervention consisting of brisk walking combined with either consumption of calorie-restricted HCLF or LCHF diet. Participants underwent a 5-hour experimental trial before and after the interventions, which included body weight measurements and fasting and postprandial blood sample collection for gastrointestinal appetite hormone measurements.Both interventions significantly reduced body mass (HCLF group, −2.1 ± 1.7 Kg: LCHF group, -1.7 ± 1.7 Kg, P < 0.05 for both groups), but changes between the groups were not significant (P>0.05). Body mass changes were individual and ranged from -0.4 kg to −5.3 kg and from +1 kg to −4.4 kg in the HCLF and LCHF groups, respectively. The interventions had no impact on mean values of time- averaged postprandial concentrations of ghrelin, PYY, and GLP-1 but there was large individual variability in changes of these hormones. Results combined from both groups revealed that changes in ghrelin ranged from +549.3 to -407.7 pg/ml, in PYY from −132.5 to + 96.4 pg/ml and in GLP-1 from −6.6 to +19.5 pg/ml. Correlation, investigated on the data from both groups combined, between changes in body mass and changes in ghrelin (r = −0.18, P= 0.41), PYY (r = −0.04, P =0.87), and GLP-1 (r = 0.11, P = 0.64) were not significant.In conclusion, the extent of body mass loss during interventions based on restricted energy intake diets combined with exercise is not related to the carbohydrate and fat content of the diet. Our findings also suggest that the success of body mass loss cannot be predicted by changes in postprandial concentrations of gastrointestinal appetite hormones.

Food temperature altered macronutrients induced changes in satiety hormones; glucagon - like peptide -1 and cholecystokinin and their correlation with subjective satiety.

The benefits of dietary macronutrients for weight management depend on the integrity of gut hormones. The role of food temperature in the release of satiety hormones and satiety needs elucidation. We aimed to determine the impact of different food temperatures with varying macronutrient compositions on satiety-related gut hormones glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) and find the correlation of satiety hormones with appetite scores and remainder-day food (energy) intake. Thirteen healthy participants (eight males and five females) aged 25-35 years with body mass index 18.5-24.9 kg/m2 with no medical illnesses or eating disorders consumed three compositions of meals (high carbohydrate, high fat, and high protein meals) each at three temperatures (cold, warm, and hot) in a randomized, double-blinded, controlled crossover design. Plasma concentrations of peptide hormones were determined at 0, 30, and 240 minutes by enzyme-linked immunosorbent assay, and 24-hours food recall was used for remainder-day food intake (remainder energy). Data were analyzed using SPSS version 27.0. The change in plasma levels of gut hormones with time was assessed using Friedman test; Kruskal-Wallis test was employed to compare GLP-1 and CCK hormonal levels across nine meals. A comparison of the three meals at the three temperatures (total of nine groups), showed that the GLP-1 and CCK plasma concentrations were significantly different (P < 0.001). GLP-1 and CCK responses increased more after hot meals than cold meals. Overall, high-fat meals had more effective gut hormone secretions. The area under the curve was increased for GLP-1 in high-fat meals and for CCK in hot meals. The peptide hormones (GLP-1 and CCK) were positively correlated with satiety scores and inversely with remainder food intake. The temperature of food was found to be an effective stimulus for the regulation of CCK and GLP-1 secretion. Hot food temperature increased satiety hormones (CCK and GLP-1), independent of food macronutrient composition.

Dietary effects of protected fat, glycerol, and soybean meal on performance, physiological parameters, carcass characteristics, and behavioral measurements of late-fattening Hanwoo steers under heat stress conditions.

This study aimed to determine the effects of increasing energy and protein levels in diets by including protected fat (PF), glycerol (GL), and soybean meal (SBM) on growth performance, physiological parameters, carcass characteristics, and behavioral measurements of late-fattening Hanwoo steers under heat stress conditions. Thirty-six steers (initial body weight, 724.9±58.3 kg; age, 25.5±0.4 month) were assigned into control (total digestible nutrient [TDN] 76%, crude protein [CP] 15%), PF (TDN 83.6%, CP 15%), PF+GL (TDN 83.6%, CP 15%) and PF+GL+SBM (TDN 83.6%, CP 16.5%) by randomized complete block design for a total of 16 weeks with division of 4-week periods. The average temperature-humidity index was 87.0 (1st period; severe), 82.8 (2nd; moderate), 71.4 (3rd; comfort), and 68.1 (4th; comfort). The dry matter intake (DMI) showed no treatments differences during the whole experiment. However, DMI in 1st and 2nd period decreased by approximately 30% and 10% compared to 4th period, respectively. Higher average daily gain and feed conversion ratio were noted for treatments compared to control at both 1st and 2nd period (p<0.05). There were no treatment effects on rectal temperature (RT), cortisol, and behaviors during the entire experiment. However, both RT and cortisol in 0, 1st and 2nd period were higher than those of 3rd and 4th period (p<0.05). Carcass yield and grade remained unaffected by increasing TDN and CP levels. Behavioral changes in the hot season (1st period) included reduced lying (43%), increased standing (48%), decreased walking (62%), and decreased eating (38%) (p<0.05), with an increase in drinking by 54%. Rumination during standing was 53% higher, while rumination during lying was about 33% lower compared to the post-hot season (3rd period) (p<0.05). Dietary supplementation of protected fat in late-fattening Hanwoo steers under heat stress had a positive effect on preventing a reduction in performance.

Chinese migrants exhibit impaired postprandial lipaemia compared to Caucasian counterparts following both high fat and high carbohydrate test meals.

People of Chinese ethnicity develop type 2 diabetes mellitus (T2DM) at a younger age and lower body mass index (BMI) than their Caucasian counterparts. Furthermore, Chinese migrants to Westernised countries have an increased risk of metabolic diseases compared to those in their country of origin(1,2). We propose that this increased risk is due to a greater manifestation of metabolic abnormalities in response to altered diet and lifestyle behaviours. Although fasting lipaemia and glycaemia are commonly used to predict risk of CVD and T2DM, assessment of impaired postprandial metabolism has been found to be a more sensitive indicator of risk(3). We hypothesised that Chinese migrants, at risk of T2DM, exhibit impaired postprandial lipid and lipoprotein metabolism compared to Australian-born Caucasian counterparts. Chinese and Caucasian adults at risk of T2DM were recruited to the study in which postprandial lipaemia and glycaemia were monitored following consumption of a high fat and high carbohydrate breakfast meal followed by a mixed, lunch meal. In a nonrandomised acute crossover trial, 15 adults (n = 8 Chinese and n = 7 Caucasian) aged ≥ 18 and ≤ 65 years at risk of T2DM (AUSDRISK score &gt; 12 (median = 14.0, IQR = 3.0)), attended two postprandial test days separated by ≥ 7-day washout period. Test breakfast meals were isocaloric (3.6 MJ), high fat (46% energy from fat, 46% energy from carbohydrates) or high carbohydrate (74% E carbohydrates, 17.5% E fat). Blood samples were collected at baseline (fasting), 180 min and 360 min after consumption of the breakfast meal. The lunch meal (3.7 MJ, 18% E fat, 76% E carbohydrates) was consumed 240 min after baseline. Samples were analysed for lipaemia and glycaemia. Additionally, chylomicron-rich, and VLDL-rich lipoprotein fractions were isolated by sequential ultracentrifugation and chylomicron particle number (apolipoprotein (apo) B48), triacylglycerol (TAG), and total cholesterol were assessed in these fractions. Data were analysed using a mixed between-within-subject analysis of variance. There were no differences in age, and baseline anthropometric measures between groups, apart from the Chinese group exhibiting significantly lower waist circumference and BMI compared to the Caucasian group. There were no differences between groups in blood measures, apart from a higher total- and LDL-cholesterol concentration in the Caucasian compared to the Chinese group (P&lt;0.05). Despite identical fasting TAG concentrations, the Chinese group, compared with the Caucasian group exhibited significantly elevated serum TAG and chylomicron-apo-B48 concentrations at 360 min following both test meals (P&lt;0.01). All other postprandial measures were not different between groups. These findings show that despite having identical or improved fasting glycaemia and lipid profile, the Chinese group exhibited impaired postprandial lipid metabolism which may contributes to their increased risk of metabolic diseases.

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review.

Oral dosage forms are the most widely and frequently used formulations to deliver active pharmaceutical ingredients (APIs), due to their ease of administration and noninvasiveness. Knowledge of intragastric release rates and gastric mixing is crucial for predicting the API release profile, especially for immediate release formulations. However, knowledge of the intragastric fate of oral dosage forms in vivo to date is limited, particularly for dosage forms administered when the stomach is in the fed state. An improved understanding of gastric food processing, dosage form location, disintegration times, and food effects is essential for greater understanding for effective API formulation design. In vitro standard and controlled modeling has played a significant role in predicting the behavior of dosage forms in vivo. However, discrepancies are reported between in vitro and in vivo disintegration times, with these discrepancies being greatest in the fed state. Studying the fate of a dosage form in vivo is a challenging process, usually requiring the use of invasive methods, such as intubation. Noninvasive, whole body imaging techniques can however provide unique insights into this process. A scoping review was performed systematically to identify and critically appraise published studies using MRI to visualize oral solid dosage forms in vivo in healthy human subjects. The review identifies that so far, an all-purpose robust contrast agent or dosage form type has not been established for dosage form visualization and disintegration studies in the gastrointestinal system. Opportunities have been identified for future studies, with particular focus on characterizing dosage form disintegration for development after the consumption food, as exemplified by the standard Food and Drug Administration (FDA) high fat meal.

Eight weeks of daily cottonseed oil intake attenuates postprandial angiopoietin-like proteins 3 and 4 responses compared to olive oil in adults with hypercholesterolemia: A secondary analysis of a randomized clinical trial

Angiopoietin-like proteins (ANGPTLs) -3, -4, and -8 are regulators of lipid metabolism and have been shown to respond to changes in dietary fats. It is unknown how ANGPTLs respond to cottonseed oil (CSO) and olive oil (OO) consumption in a population with hypercholesterolemia. The purpose of this study was to determine the impact of CSO vs. OO consumption on fasting and postprandial ANGPTL responses in adults with hypercholesterolemia. We hypothesized that CSO would have lower fasting and postprandial ANGPTL responses compared with OO. Forty-two adults with high cholesterol completed a single-blind, randomized trial comparing CSO (n = 21) vs. OO (n = 21) diet enrichment. An 8-week partial outpatient feeding intervention provided ∼60% of the volunteers’ total energy expenditure (∼30% of total energy expenditure as CSO or OO). The remaining 40% was not controlled. Fasting blood draws were taken at pre-, mid-, and postintervention visits. Volunteers consumed a high saturated fat meal followed by 5 hours of blood draws pre- and postvisits. Fasting ANGPTL3 had a marginally significant treatment by visit interaction (P = .06) showing an increase from pre- to postintervention in CSO vs. OO (CSO: 385.1 ± 27.7 to 440.3 ± 33.9 ng/mL; OO: 468.2 ± 38.3 to 449.2 ± 49.5 ng/mL). Both postprandial ANGPTL3 (P = .02) and ANGPTL4 (P < .01) had treatment by visit interactions suggesting increases from pre- to postintervention in OO vs. CSO with no differences between groups in ANGPTL8. These data show a worsening (increase) of postprandial ANGPTLs after the OO, but not CSO, intervention. This aligns with previously reported data in which postprandial triglycerides were protected from increases compared with OO. ANGPTLs may mediate protective effects of CSO consumption on lipid control. This trial was registered at clinicaltrials.gov (NCT04397055).

The Effect of Fat Supplementation on the Appearance of Symptoms Associated With Dumping Syndrome in Patients Having Undergone Gastric Surgery: Preliminary Results.

Data on the effect of dietary fat on dumping syndrome (DS) symptoms are limited. The aim of this study was to assess the effect of the addition of fat to a carbohydrate mealon the appearance of DS symptoms and glycemic response, in patients who had undergone gastric surgery. This was an interventional crossover study. Patients scheduled for gastric surgical procedures related to DS at two surgical units of two public hospitals (General University Hospital of Larissaand General Hospital of Larissa)were considered for study inclusion. Patients presenting symptoms suggestive of diagnosis (n = 12), after the ingestion of a carbohydrate meal, were used as both intervention and control groups. During the intervention process, a fat supplement was added to the carbohydrate meal that was previously used for diagnosis. Glycemic response and the amount and intensity of DS symptoms provoked by the two meals were assessed at both appointments. Blood glucose levels were significantly lower in the group that consumed the added fat meal compared with the group that consumed the carbohydrate meal 60 minutes after ingestion (p = 0.028). Furthermore, a significant reduction was noted in the amount of late dumping symptoms (p = 0.021)and the intensity of both early and late dumping symptoms (p = 0.007 and p = 0.012 respectively), after fat addition. Conclusions: Incorporating fat into a carbohydrate meal seems toattenuate postprandial blood glucose risesand reduce the amount and intensity of DS symptoms, in patients who had undergone gastric surgery.

An acute exercise at low to moderate intensity attenuated postprandial lipemia and insulin responses

ObjectiveThe purpose of this study was to investigate the effects of different exercise intensities on postprandial lipemia (PHTG) and insulin resistance in healthy individuals. MethodsParticipants were 10 adult males with normal fasting triglyceride (TG) concentrations (age = 34 ± 2.8 y, body mass = 72.9 ± 2.4 kg, fasting plasma TG = 1.36 ± 0.18 mmol/l, VO2max = 43.7 ± 3.0 ml/kg/min, fasting glucose = 5.2 ± 0.2 mmol/l and fasting Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR) = 1.7 ± 0.3). In this study, each participant performed a control trial (Ctr, no exercise), and 3 exercise trials at 40 % (40%T), 60 % (60%T), and 70 % (70%T) of their VO2max. In the exercise trials, participant jogged on a treadmill for 1 h at a designated intensity. A fat-rich meal was consumed by each participant 12 h after exercise. Blood samples were taken at 0 h (before the meal), and 2 h, 4 h, 6 h, 8 h, and 24 h after the meal. The plasma TG, area score under TG concentration curve over an 8 h-period (TG tAUC) after the meal, and HOMA2-IR were analyzed. ResultsOur results showed that at 2 h, 4 h, and 6 h after the meal, TG in all exercise trials were lower than Ctr (p < 0.05) but did not differ from each other. All the exercise trials were lower in TG tAUC scores than Ctr (p < 0.02), but differences were not observed among the exercise trials. In comparison to Ctr, a significant difference in HOMA2-IR in both 60 % T and 70 % T (p < 0.05 and p < 0.01, respectively) was observed, but not in 40 % T. ConclusionThe results suggest that exercising at low to moderate exercise intensity for 1 h sufficiently attenuates a fat meal induced PHTG. Moderate exercise intensity also effectively mitigates insulin resistance.

Splitting Mealtime Insulin Doses for Mixed Fat and Protein Meals in Children and Adolescents with Type 1 Diabetes Using Multiple Daily Injection Regimen: A Randomized Cross-Over Trial

Aims. Assessment of the glycemic outcomes of increasing and splitting mealtime insulin doses for mixed fat and protein meals in pediatric patients with type 1 diabetes mellitus (T1DM) using multiple daily injection regimen and comparing the effects of regular insulin and fast-acting insulin on glycemic outcomes following those meals. Methods. This single-center, randomized, cross-over trial included 43 children and adolescents with T1DM randomly assigned to receive three interventional insulin doses for lunch meals over 3 consecutive days; Intervention A (100% insulin-to-carbohydrate ratio (ICR) dose given as premeal insulin lispro with an additional insulin sensitivity factor-calculated correction dose after 3 hr), Intervention B (130% ICR dose split into 60% premeal insulin lispro and 40% postmeal insulin lispro after 30 min), and Intervention C (130% ICR dose split into 60% premeal insulin lispro and 40% postmeal regular insulin after 30 min). The test meal consisted of two slices of pizza (weight: 150 g, carbohydrates: 40 g, fat: 15 g, protein: 20 g, and calories: 380 kcal). Postprandial blood glucose levels were monitored for 6 hr. Results. There were no significant differences in postprandial blood glucose excursions following the three interventions. However, Intervention C had a significantly lower late (3–6 hr) blood glucose area under the curve ( p = 0.01 ). Postprandial hypoglycemia developed in 12 participants (27.9%) following Interventions A and B and in 17 participants (39.5%) following Intervention C ( p = 0.32 ). Conclusions. Using regular insulin as a postmeal portion of increased and split insulin doses provided better late postprandial glycemic outcomes following mixed fat and protein meals. However, the amount of additional insulin used needs optimization to reduce the frequency of postprandial hypoglycemia. This trial is registered with NCT04783376.

Measures to reduce sugar, fat, and salt content of food and beverages in selected European countries

Abstract Introduction Improving food environments to promote healthy diets is a core element of many nutrition and health policies. Government-driven attempts at achieving such improvements comprise mandatory and voluntary measures to reduce the content of sugar, fat, and salt in food and beverages. Here we provide an overview of the different measures taken in selected European countries. Methods A systematic internet search for ongoing or planned national reduction measures in each of the three categories of taxation, legal limits/bans, and self-commitments was conducted for 19 European countries. Core characteristics of each measure, including evaluations thereof, were extracted and summarized. Results The measures varied in, e.g., the nutrients, product groups, and sectors addressed (manufacturing, retail, out-of-home), the timeframe, and the target values. Taxation (15 countries) mainly concerned sweetened beverages, with tax levels mostly depending on the sugar content. Independent evaluations concluded that the tax introduction had led to the sugar content being reduced as well as consumer demand shifted towards lower-sugar options. Six countries had legal limits for the salt content in bread (limits between 1.3 g and 2 g/100 g bread), and nine countries set legal limits for sugar, fat, and salt in food or meals or vending bans for products high in these nutrients in food service for the public sector. The limited evaluations of compliance with the upper limits were ambivalent. Voluntary commitments (12 countries) mainly concerned the reduction of salt and sugar. Independent studies and monitoring results on the achievement of the agreements showed mixed results. Conclusions National measures to reduce sugar, fat, and salt in food and drinks varied in content and depth, and thus in their likely ability to contribute to a healthier food environment. More comprehensive monitoring and evaluation is needed to better assess the effectiveness of the different approaches.

Efficacy of the MiniMed™ 670G hybrid closed loop system in managing postprandial glucose excursion with high protein high fat foods in children and adolescents under free-living conditions

Objectives: High protein high fat (HPHF) meals are considered “difficult” foods because they can cause prolonged hyperglycemia after ingestion. The potential of hybrid closed loop therapy in managing postprandial glucose excursions with these difficult foods remains unknown. This pilot study aimed to explore the impact of manual mode in standard insulin pump therapy and auto mode with hybrid closed loop pump therapy in managing glucose excursions caused by HPHF foods and to obtain feedback from families about each mode. Material and Methods: Children and adolescents (8–18 years) with type 1 diabetes and using the MiniMed™ 670G were recruited to a free-living randomized cross-over study. Participants consumed a standardized lasagne or pizza meal two nights a week for 4 weeks while in auto mode and manual mode. Postprandial continuous glucose monitoring data were collected for 7 h post-meal. The primary outcomes were mean postprandial net incremental area under the glucose × time curve. User experiences were collected during end-of-study interviews administered to parents. Results: Postprandial excursions from 38 meals in seven participants were analyzed. There were no significant differences between auto mode and manual mode for the mean net incremental area under the glucose × time curve, irrespective of meal type. Semi-structured end-of-study interviews revealed that five of seven families felt more confident eating HPHF meals in auto mode. Conclusion: Although most families felt confident with auto mode for postprandial HPHF excursions, this was not reflected in the postprandial glucose levels.

The LIPL study: Postprandial lipid profile, inflammation, and platelet activity in patients with chronic coronary syndrome

Background and aimsIt is suggested that the changes in atherosclerosis happen mainly under the influence of non-fasting lipids. To date, the studies in the postprandial state were primarily performed on healthy subjects. This exploratory, cross-sectional study investigates the change in lipid profile, inflammation, and platelet activation in patients with different cardiovascular risk profiles in the postprandial state. MethodsThe studied population consists of 66 patients with different cardiovascular risks: patients with a history of the chronic coronary syndrome (CCS) and diabetes mellitus type 2 (DM2) (n = 20), CCS without DM2 (n = 25), and a healthy control group (n = 21). Lipid variables and markers of platelet function and inflammation were assessed during the fasting state and three and 5 h after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90 g of fat. ResultsPatients with CCS and DM2 were significantly older and had the highest BMI. All patients with CCS were on acetylsalicylic acid, and 95% of CCS patients were on high-dose statins. The absolute leukocyte and neutrophile count increased significantly in the control group during the OFTT in comparison to CCS subjects. There was a significant decrease of HDL and increase of triglycerides during the OFTT, however with no difference between groups. There was no difference in the change of platelet activity between all groups. ConclusionThis study showed that OFTT leads to an increased postprandial inflammation response in healthy group compared to CCS ± DM2 while there was no change in lipid profile and platelet activity.

Effect of food and polymorphisms in SLCO2B1, CYP3A4 and UGT1A4 on pharmacokinetics of abiraterone and its metabolites in Chinese volunteers.

Abiraterone acetate, a prodrug of abiraterone (ABI), provides an efficient therapeutic option for metastatic castration-resistant prostate cancer patients. ABI undergoes extensive metabolism in vivo and is transformed into active metabolites Δ4 -abiraterone and 3-keto-5α-abiraterone as well as inactive metabolites abiraterone sulfate and abiraterone N-oxide sulfate. We aimed to examine the effect of polymorphisms in SLCO2B1, CYP3A4 and UGT1A4 on the pharmacokinetics of ABI and its metabolites. In this study, 81 healthy Chinese subjects were enrolled and divided into 2 groups for fasted (n = 45) and fed (n = 36) studies. Plasma samples were collected after administering a 250 mg abiraterone acetate tablet followed by liquid chromatography-tandem mass spectrometry analysis. Genotyping was performed on a MassARRAY system. The association between SLCO2B1, CYP3A4, UGT1A4 genotype and pharmacokinetic parameters of ABI and its metabolites was assessed. Food effect study demonstrated high fat meal remarkedly increased systemic exposure of ABI and its metabolites. The geometric mean ratio and 90% confidence interval of area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration(AUC0-t ) and maximum plasma concentration (Cmax ) of ABI in fed state vs. fasted state were 351.64% (286.86%-431.04%) and 478.45% (390.01%-586.94%), respectively, while the corresponding results were ranging from 145.11% to 269.42% and 150.10% to 478.45% for AUC0-t and Cmax of ABI metabolites in fed state vs. fasted state, respectively. The SLCO2B1 rs1077858 had a significant influence on AUC0-t and Cmax , while 7 other SLCO2B1 variants prolonged half-life of ABI under both fasted and fed conditions. As for ABI metabolites, the systemic exposure of Δ4 -abiraterone, abiraterone sulfate and abiraterone N-oxide sulfate as well as the elimination of 3-keto-5α-abiraterone were significantly affected by SLCO2B1 polymorphisms. Polymorphisms in CYP3A4 and UGT1A4 did not significantly affect pharmacokinetics of ABI and its metabolites. Polymorphisms in SLCO2B1 were significantly related to the pharmacokinetic variability of ABI and its metabolites under both fasted and fed conditions.

A 4-Week Pecan-Enriched Diet Improves Postprandial Lipid Peroxidation in Aging Adults.

Pecans are rich in bioactive compounds known to reduce oxidative stress and provide glucoregulatory benefits. Few studies assessing the effect of a pecan-enriched diet on such health outcomes suggest potential improvements to cardiometabolic health; however, this has not been studied in an older adult population. Thus, we aimed to examine the effect of daily pecan consumption for 4-weeks on fasting and postmeal antioxidant status, oxidative stress, and markers of glycemia in healthy aging adults. In this randomized, parallel, controlled trial, 41 healthy adults (50-75 years) either consumed 68 g of pecans/day (pecan; n = 21) or avoided all nuts (control; n = 20). At pre- (V1) and postintervention visits (V2), blood samples were obtained at fasting, and 30, 60, and 120 min following a high saturated fat meal to assess changes in malondialdehyde, which is a measure of lipid peroxidation, total antioxidant capacity (TAC), glucose, and insulin. Across the intervention, there were no differences in fasting or postprandial TAC, glucose, or insulin for pecan versus control. There was a trend for a difference in fasting lipid peroxidation from V1 to V2 by treatment (P = .06) driven by a slight reduction for pecan versus control (Δpecan: -2.0 ± 1.1 vs. Δcontrol: +0.6 ± 0.8 μM). In addition, postprandial lipid peroxidation was suppressed at V2 for pecan, and this was different from control (pecan areas under the curve (AUC): 10.6 ± 1.3 μM/h to 9.1 ± 1.2 μM/h vs. control AUC: 8.9 ± 1.3 μM/h to 9.2 ± 1.1 μM/h; P = .03). These findings suggest that a 1 month, pecan-enriched diet is protective against postmeal oxidative stress. Longer interventions or a diabetic population may be needed to observe glucoregulatory benefits. Clinical Trial Registration: NCT04385537.

Post-prandial secretion of glucagon-like peptide-2 (GLP-2) after carbohydrate-, fat- or protein enriched meals in healthy subjects

Glucagon-like peptide 2 (GLP-2) is an important regulator of intestinal growth and function. In adherable mixed meals the macronutrient composition with the best potential for stimulating GLP-2 secretion is not known. We compared the effect of 3 iso-energetic meals, where approximately 60 % of the energy ratio was provided as either carbohydrate, fat, or protein, respectively, on the post-prandial endogenous GLP-2 secretion. The responses were compared to secretion profiles of peptide YY (PYY), and glucose-dependent insulinotropic peptide (GIP).Ten healthy subjects were admitted on three occasions, at least a week apart, after a night of fasting. In an open-label, crossover design, they were randomized to receive a high carbohydrate (HC), high fat (HF) or high protein (HP) meal. The meals were approximately ∼3.9 MJ. Venous blood was collected for 240 min, and plasma concentrations of GLP-2, GIP and PYY were measured with specific radioimmunoassays.Mean GLP-2 levels peaked already at 30 min for the HC meal, however the HP meal induced the highest mean GLP-2 peaking levels, resulting in significantly higher mean GLP-2 area under the curve (AUC) from baseline of 7279 pmol*min/L, 95 %-CI [6081;8477] compared to the HC meal: 4764 pmol*min/L, 95 %-CI [3498;6029], p = 0.020 and the HF meal: 4796 pmol*min/L, [3385;6207], p = 0.011. Findings were similar for the PYY. The HC meal provided a greater AUC for GIP compared to the HP- and HF meals.The HP meal was most effective with respect to stimulation of the postprandial GLP-2 and PYY secretion, whereas the HC meal was more effective for GIP.

Comparing dehulled hemp meal and canola meal as a protein supplement for lactating dairy cows

Effects of replacing canola meal with dehulled hemp meal in the diet of lactating dairy cows on the dry matter intake (DMI), milk production, milk fatty acid profile, blood metabolites, total-tract nutrient digestibility, and transfer of cannabinoids were determined in 12 lactating, nonpregnant Holstein cows. These cows were used in a 3 × 3 Latin square design with three 3-wk experimental periods consisting of 2 wk of adaptation and 1 wk of sampling. Cows received basal partial mixed rations supplemented with either 15% dry matter (DM) canola meal (CM15), 15% DM dehulled hemp meal (HM15), or 7.5% DM dehulled hemp meal and 7.5% DM canola meal (CM7.5HM7.5). Diets were formulated to be isoenergetic and isonitrogenous, but the HM15 and CM7.5HM7.5 diets contained, on average 1.2 percentage units more crude protein (CP) that the CM15 diet. The CP of the dehulled hemp meal contained less soluble protein than that of canola meal. Hence, the intake of soluble protein did not differ among diets. Canola meal contained less crude fat than hemp seed meal (3.46% vs. 8.25% DM). The lipid fraction of canola meal fat contained more oleic acid (C18:1 cis-9; 47.3 vs. 14.9 g/100 g of fatty acids, FA) and vaccenic acid (18:1 cis-11; 13.7 vs. 1.2 g/100 g of FA) and less linoleic acid (C18:2n-6; 21.9 vs. 55.7 g/100 g of FA) and α linolenic acid (C18:3n-3; 3.2 vs. 8.9 g/100 g of FA) than the lipid fraction of hemp seed meal. The hemp seed meal contained 4.9 µg/g cannabidiol, 5.1 µg/g cannabidiolic acid, and 0.1 µg/g tertahydroxycannabinolic acid A. Treatments did not differ in DMI, yields of milk, milk protein and milk fat, total-tract neutral detergent fiber digestibility, and blood plasma concentrations of β-hydroxybutyrate and nonesterified FA. Apparent total-tract DM digestibility was lowest in the HM15 treatment, whereas the CP digestibility and the concentrations of urea in blood, urine, and milk were lowest in the CM15 treatment. Cannabinoids were not detected in urine, milk, and blood plasma. Replacing canola meal with hemp seed meal increased milk fat contents of polyunsaturated fatty acids (PUFA), which were 3.42, 3.90, and 4.25 g/100 g of FA for the CM15, CM7.5HM7.5, and HM15 treatments, respectively. Especially, the milk fat contents of 18:2n-6 (1.99 vs. 1.56 g/100 g FA) and 18:3n-3 (0.31 vs. 0.43 g/100 g FA) were increased by hemp meal feeding. Especially, the milk fat contents of 18:2n-6 (1.99 vs. 1.56 g/100 g FA) and 18:3n-3 (0.31 vs. 0.43 g/100 g FA) were increased by hemp meal feeding. Our data show that hemp seed meal is a suitable and safe replacement for canola meal as a feed for lactating dairy cows and that this replacement increases CP digestibility and urea in urine, milk, and blood plasma, as well the PUFA content of milk fat.

A Novel Functional Refined Olive Oil, Enhanced with Orange Peel Extract, Modulates Postprandial LDL-Cholesterol Responses in Individuals at Cardiometabolic Risk: A Pilot Randomized, Controlled, Cross-Over Nutritional Intervention

Olive oil, as the main source of polyphenols in the Mediterranean diet pattern, is mentioned to show remarkable postprandial bioactivity, contributing to the reduction of cardiometabolic risk factors. In recent years, the consumption of refined olive oil, instead of other olive oil classes, led to a reduced intake of polyphenols from the usual diet. This controlled, human nutritional intervention investigated whether the enhancement of refined olive oil with orange peel extract may modulate postprandial lipemia, glycemia, and oxidative stress in individuals at cardiometabolic risk. In a cross-over framework, 21 participants aged 30–65 years, who met the eligibility criteria, received a fat and carbohydrate meal of mashed potatoes, homogenized with refined olive oil (50 mL) or the functional olive oil, enhanced with 10% orange peel extract, intervening a washout week. Blood draws were performed in fasting, 30 min, 1.5 h, and 3 h after the meal intake. Plasma lipids, glucose, uric acid, and total plasma antioxidant capacity, according to the FRAP method, were measured at each timepoint. A significant reduction of LDL-cholesterol was observed, 1.5 h and 3 h after the functional meal intake, compared to non-significant changes after the control meal (p &lt; 0.05). No other statistically significant interactions were detected to the remaining biomarkers (p &gt; 0.05). Further investigation is needed for safer conclusions about the postprandial modulation of cardiometabolic risk factors by the functional olive oil enhanced with orange peel extract.

754-P: A First-in-Human Single Ascending Dose Study of GSBR-1290, a Novel Small Molecule GLP-1 Receptor Agonist, in Healthy Volunteers

Introduction: Type 2 Diabetes Mellitus (T2DM) and obesity incidences are rising globally. The risk:benefit ratio of peptide GLP-1 receptor agonists (RAs) has been established; however, new therapeutic options are still needed. We report the results of a single ascending dose (SAD) study with GSBR-1290, a highly potent, orally bioavailable, fully biased small molecule GLP-1 RA. Methods: The study enrolled 48 healthy volunteers in 6 Cohorts, randomized 3:1 to receive GSBR-1290 (1, 10, 15, 30, 60, and 90 mg) or placebo, under fasting conditions. The safety, tolerability, and pharmacokinetics (PK) of a single dose of GSBR-1290 were investigated. The food effect on PK was also assessed in the 15 mg cohort. Results: Participants were well-balanced across the treatment groups: female (60%), white (66%), mean age (SD) 30 (8) years, and BMI (SD) 24.5 (3.0). All randomized subjects completed the study and there were no deaths or serious adverse events. Treatment-emergent adverse events (TEAEs) were reported for 32/36 participants (89%) following fasted administration of GSBR-1290 and for 7/12 participants (58%) following administration of placebo. The majority (94%) were mild or moderate in severity. As expected, the most common TEAEs were gastrointestinal-related and included nausea, vomiting, decreased appetite and diarrhea, consistent with other drugs in this class. No clinically significant changes in laboratory safety parameters were reported. PK (Cmax and AUC) of GSBR-1290 increased with dose, and a high fat meal was associated with a 20% decrease in the geometric mean AUC and a 36% decrease in Cmax. Conclusion: GSBR-1290 is a promising orally available GLP-1 RA and was well-tolerated in this SAD study in healthy volunteers. These data support further clinical development in a multiple ascending dose study in individuals with T2DM and obesity. Disclosure B.Coll: Employee; Amgen Inc., ShouTi Pharma Inc. J.J.Zhang: Employee; Structure Therapeutics Inc. S.J.Jacober: Consultant; Structure Therapeutics, Inc., Adocia, Employee; Sanofi-Aventis U.S., Applied Therapeutics Inc., Other Relationship; Eli Lilly and Company. C.Argent: None. L.Ibarra: Employee; Structure Therapeutics. M.Snyder: None. M.A.Bach: Employee; Structure Therapeutics, Stock/Shareholder; Johnson &amp; Johnson. Funding Structure Therapeutics Inc.