Postprandial Plasma Triglyceride Research Articles

Effects on cardiovascular risk factors of a low- vs high-glycemic index Mediterranean diet in high cardiometabolic risk individuals: the MEDGI-Carb study.

The role of dietary Glycemic Index (GI), independently of fiber intake, in modulating cardiovascular disease (CVD) risk among non-diabetic individuals has not been fully elucidated. To evaluate the effects of a low- versus a high-GI diet, based on a Mediterranean dietary pattern, on cardiometabolic risk factors in individuals at high CVD risk, participating in the MEDGI-Carb intervention study. 160 individuals, aged 30-69 years, BMI 25-37 kg/m2, with a waist circumference >102 cm (males) or >88 cm (females) and one feature of the metabolic syndrome, participated in a multi-national (Italy, Sweden, USA) randomized controlled parallel group trial. Participants were assigned to a low GI (< 55) or high-GI MedDiet ( > 70) for 12 weeks. The diets were isoenergetic and similar for available carbohydrate (270 g/d) and fiber (35 g/d) content. Fasting metabolic parameters were evaluated in the whole cohort, while an 8-h triglyceride profile (after standard breakfast and lunch) was evaluated only in the Italian cohort. Blood pressure and most fasting metabolic parameters improved at the end of the dietary intervention (time effect, p < 0.05 for all); however, no differences were observed between the low- and the high-GI MedDiet groups (time x group effect; p > 0.05 for all). Conversely, the low-GI diet, compared with high-GI diet, significantly reduced the 8-h triglyceride profile (p < 0.017, time*group effect) that was measured only in the Italian cohort. However, it induced a reduction of plasma triglycerides after lunch (tAUC) that was of only borderline statistically significance (p = 0.065). Consuming a low-GI in comparison with a high-GI MedDiet does not differentially affect the major cardiometabolic risk factors at fasting in individuals at increased cardiometabolic risk. Conversely, it could reduce postprandial plasma triglycerides. NCT03410719, ( https://clinicaltrials.gov ).

Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 2 - Biliopancreatic Diversion.

Obesity significantly increases the risk of developing metabolic and cardiovascular diseases. The most effective management tool for both obesity and type 2 diabetes (T2D) is bariatric/metabolic surgery. Delayed postprandial plasma triglyceride clearance contributes to the development of atherosclerosis in patients with T2D. Biliopancreatic diversion (BPD) was shown to be the most effective procedure in long-term T2D remission. However, the effect of BPD on postprandial metabolic profile has not been studied so far. In this pilot study, we therefore examined the changes in postprandial glucose, insulin, and triglyceride in women with severe obesity and T2D before surgery and then two and ten years after BPD. The studied cohort included 7 women (mean age at baseline=49.3±8.2 years) with severe obesity (mean BMI= 45.7±2.9 kg/m?) and T2D. A standardized liquid mixed-meal test was carried out in all subjects and the mean postprandial levels of plasma glucose, insulin, and triglyceride were analyzed by standard laboratory procedures. For statistical evaluation, ANOVA with Bonferroni multiple comparisons was used. Ten years after BPD not only a significant reduction of an average BMI (F=32.9, p<0.001) but also significant declines in mean postprandial plasma levels of glucose (F=155.3, p<0.001), insulin (F=69.8, p<0.001), and triglyceride (F=139.9, p<0.001) were demonstrated. The observed changes in postprandial metabolic profile may contribute to improved cardiometabolic health after bariatric surgery.

Milk fat globule membrane modulates inflammatory pathways in human monocytes: A crossover human intervention study

BackgroundIntake of high-fat foods raises postprandial plasma triglycerides and inflammatory markers, which may depend on the type of fat ingested. Dairy products are commonly consumed, but not much is known about the impact of milk fat and the milk fat globule membrane on postprandial inflammation. Here, we aimed to study the effect of milk fat with and without milk fat globule membrane and vegetable blend fat on post-prandial inflammation, with a focus on blood monocyte gene expression. MethodsWe performed a randomized, double-blind cross-over trial in 37 middle-aged healthy male and female volunteers (BMI 22-27 kg/m2). The participants consumed a meal shake containing 95.5 g of fat consisting of either a vegetable fat blend (VEGE), anhydrous milk fat (AMF, without milk fat globule membrane), or cream (CREAM, containing milk fat globule membrane). Blood monocytes were collected at 0 hours and 6 hours postprandially and used for bulk RNA sequencing and ex vivo stimulation with LPS. ResultsConsumption of all three shakes significantly decreased the percentage of classical monocytes and increased the percentages of intermediate monocytes and non-classical monocytes. No differences in these measures were observed between shakes. Using a threshold of P<0.01, 787 genes were differentially regulated postprandially between the three shakes. 89 genes were differentially regulated postprandially between AMF and VEGE, 373 genes between AMF and CREAM, and 667 genes between VEGE and CREAM, indicating that the effect of CREAM on monocyte gene expression was distinct from AMF and VEGE. Pathway analyses showed that VEGE significantly increased the expression of genes involved in inflammatory pathways, whereas this was less pronounced after AMF and not observed after CREAM. In addition, CREAM significantly down-regulated the expression of genes involved in energy metabolism-related pathways, such as glycolysis, TCA cycle, and oxidative phosphorylation, as well as HIF1 signaling. ConclusionCompared to the consumption of an anhydrous milk fat without milk fat globule membrane and a vegetable fat blend, the consumption of cream with milk fat globule membrane downregulated inflammatory pathways in blood monocytes, thus suggesting a potential inflammation inhibitory effect of milk fat globule membrane.

Evaluating the relation between serum apolipoprotein B (apo B), apolipoprotein A (apo A) and apo B/apo A ratio with diabetic retinopathy in a sample of type 2 Egyptian diabetic patient

BackgroundDiabetic retinopathy (DR) is a chronic progressive, ocular disease affecting the retinal microvasculature accompanied by hyperglycaemia and different situations related to diabetes mellitus (DM) such as hypertension (HTN). Till now, the majority of researches demonstrated an insignificant correlation between lipid profile parameters and DR. Novel serum lipid markers (apolipoproteins) which are the protein portion of lipoproteins were recently linked to DR, and observed that the increased apo B and high apo B/apo A ratio accompanied by a higher possibility of proliferative DR.AimTo assess the relation between novel serum lipid markers and various grades of DR in a sample of type 2 Egyptian diabetic cases.MethodsThis study comprised 80 cases with type 2 diabetes mellitus (T2DM) divided into 3 groups: T2DM cases with proliferative diabetic retinopathy (PDR) (group I), T2DM cases with non-PDR (group II) and T2DM cases without DR as a control group (group III). Fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2hpp), haemoglobinA1c (HbA1c), cholesterol (chol), triglycerides (TG), LDL, HDL and serum apolipoprotein A and B level. Complete medical history was taken from entire cases with a special focus on the duration of HTN and diabetes and full clinical examination (including BP and BMI).ResultsThere was a significant difference regarding serum apo B, apo B/apo A ratio, TG, total chol, LDL (p<0.001*), DM duration (p=0.002), HTN duration (p=0.014), SBP (p=0.006), DBP (p=0.013), BMI (p=0.050) and HbA1c (p=0.025), being higher in group I than group II than group III; also, there was a significant difference between them with regard to serum apo A (p=0.010), and HDL (p=0.047) being higher in group III than group II than group I.On comparing group I with group II using Post hock Tukey’s test there was a significant difference regarding serum apo B (p=.023) and apo B/apo A ratio (p=.002).There was a statistically significant positive correlation between serum apo B/apo A ratio and diabetic duration (r=0.248), HTN d (r=0.4), HbA1c (r=.47), LDL (r=0.68), triglycerides (r=0.52), cholesterol (r=0.70) and a statistically significant negative correlation between serum apo B/apo A ratio and HDL (r=0.37) in all subjects. In addition, HTN duration was demonstrated to be the most independent factor affecting B/A ratio.ConclusionSerum apo B and serum apo B/apo A ratio in diabetic cases are higher in the presence of retinopathy, triglycerides, total cholesterol, LDL, and HDL, and it is also higher in proliferative than non-proliferative diabetic retinopathy. The current study emphasizes on the potential correlation between the high serum apo B, serum apo B/apo A ratio and the advancement of DR.

Acute Statin Withdrawal Does not Interfere With the Improvements of a Session of Exercise in Postprandial Metabolism.

The risk for atherogenic plaque formation is high after ingestion of meals in individuals with high blood lipid levels (ie, dyslipidemia). Statins and exercise reduce the rise of blood triglyceride concentrations after a meal, but the effect of their combination is unclear. In a randomized crossover design, 11 individuals with dyslipidemia and metabolic syndrome treated with statins underwent a mixed-meal (970 ± 111 kcal, 24% fat, and 34% carbohydrate) tolerance test. Plasma lipid concentrations, fat oxidation, glucose, and glycerol kinetics were monitored immediately prior and during the meal test. Trials were conducted with participants under their habitual statin treatment and 96 hours after blinded statin withdrawal. Trials were duplicated after a prolonged bout of low-intensity exercise (75 minutes at 53 ± 4% maximal oxygen consumption) to study the interactions between exercise and statins. Statins reduced postprandial plasma triglycerides from 3.03 ± 0.85 to 2.52 ± 0.86 mmol·L-1 (17%; P = .015) and plasma glycerol concentrations (ie, surrogate of whole-body lipolysis) without reducing plasma free fatty acid concentration or fat oxidation. Prior exercise increased postprandial plasma glycerol levels (P = .029) and fat oxidation rates (P = .024). Exercise decreased postprandial plasma insulin levels (241 ± 116 vs 301 ± 172 ρmol·L-1; P = .026) but not enough to increase insulin sensitivity (P = .614). Neither statins nor exercise affected plasma glucose appearance rates from exogenous or endogenous sources. In dyslipidemic individuals, statins reduce blood triglyceride concentrations after a meal, but without limiting fat oxidation. Statins do not interfere with exercise lowering the postprandial insulin that likely promotes fat oxidation. Last, statins do not restrict the rates of plasma incorporation or oxidation of the ingested glucose.

Blood Lipid Responses to Diets Enriched with Cottonseed Oil Compared with Olive Oil in Adults with High Cholesterol in a Randomized Trial

BackgroundIncreasing unsaturated fat intake is beneficial for cardiovascular health, but the type of unsaturated fat to recommend remains equivocal. ObjectivesWe investigated the effects of an 8-week diet intervention that was rich in either cottonseed oil (CSO; PUFA rich) or olive oil (OO; MUFA rich) on blood lipids in hypercholesterolemic adults. MethodsForty-three men and women with hypercholesterolemia (53 ± 10 years; BMI, 27.6 ± 4.8 kg/m2) completed this randomized parallel clinical trial consisting of an 8-week partial outpatient feeding intervention. Participants were given meals and snacks accounting for ∼60% of their daily energy needs, with 30% of energy needs from either CSO (n = 21) or OO (n = 22). At pre- and postdiet intervention visits, participants consumed a high-SFA meal (35% of total energy needs; 70% of energy from fat). The primary outcomes of fasting cholesterol profiles and secondary outcomes of postprandial blood lipids and glycemic markers were assessed over a 5-hour period. ResultsThere were greater reductions from baseline to week 8 in fasting serum total cholesterol (TC; −17.0 ± 3.94 mg/dL compared with −2.18 ± 3.72 mg/dL, respectively; P = 0.008), LDL cholesterol (−19.7 ± 3.94 mg/dL compared with −5.72 ± 4.23 mg/dL, respectively; P = 0.018), non–HDL cholesterol (−20.8 mg/dL ± 4.00 compared with −6.61 ± 4.01 mg/dL, respectively; P = 0.014), and apoB (−11.8 mg/dL ± 2.37 compared with −3.10 ± 2.99 mg/dL, respectively; P = 0.05), in CSO compared with OO. There were also visit effects from baseline to week 8 for increases in HDL cholesterol (CSO, 56.5 ± 2.79 mg/dL to 60.2 ± 3.35 mg/dL, respectively; OO: 59.7 ± 2.63 mg/dL to 64.1 ± 2.24 mg/dL, respectively; P < 0.001), and decreases in the TC:HDL-cholesterol ratio (CSO, 4.30 ± 0.27 mg/dL to 3.78 ± 0.27 mg/dL, respectively; OO, 3.94 ± 0.16 mg/dL to 3.57 ± 0.11 mg/dL, respectively; P < 0.001), regardless of group assignment. In response to the high-SFA meal, there were differences in postprandial plasma glucose (P = 0.003) and triglyceride (P = 0.004) responses and a trend in nonesterified fatty acids (P = 0.11) between groups, showing protection in the postprandial state from an occasional high-SFA fat meal with CSO, but not OO, diet enrichment. ConclusionsCSO, but not OO, diet enrichment caused substantial improvements in fasting and postprandial blood lipids and postprandial glycemia in hypercholesterolemic adults. This trial was registered at clinicaltrials.gov as NCT04397055.

Intrauterine Growth-Restricted Piglets Are Predisposed to Develop Metabolic Disorders in Adulthood When Fed With Parenteral Nutrition in the Neonatal Period

ObjectivesTotal parenteral nutrition (TPN) is lifesaving yet non-normal nutrition regimen during the neonatal period. However, studies have shown that TPN feeding early in life can permanently alter metabolism at later ages. Moreover, intrauterine growth restricted (IUGR) neonates also have a higher risk of developing metabolic diseases (such as obesity and dyslipidemia) in later life. Because a substantial proportion of IUGR neonates receive TPN in early life, we wondered if the metabolic effects of feeding TPN early in life would exacerbate these effects of IUGR? We hypothesized that feeding TPN to IUGR neonates would aggravate the risk of developing obesity and dyslipidemia in adulthood.MethodsSixteen normal weight female piglets (7 d old) were randomized to sow-fed (SF) or early TPN (TPN-CON); 8 (IUGR or runt) piglets were fed TPN as a third group (TPN-IUGR). After 2 weeks of TPN or suckling, all pigs were fed a normal grower diet for 8 mo. At 8 mo, catheters were implanted and in vivo metabolic tests were conducted.ResultsTPN-IUGR pigs demonstrated catch-up growth by 4 mo, and body weights were not different among groups at 8 mo. The metabolic effects of feeding TPN persisted into adulthood, as indicated by higher postprandial plasma triglycerides (TG) and fasting plasma non-esterified fatty acids (NEFA), compared to SF (P < 0.05). IUGR exacerbated TPN-induced risk for diseases by worsening obesity outcomes with greater subcutaneous fat deposition (P < 0.05) and greater ectopic TG deposition in the liver (P < 0.05) and muscle (P < 0.05). Furthermore, IUGR led to dyslipidemia as indicated by higher cholesterol in fasted plasma LDL (P < 0.05), slower postprandial TG clearance (P < 0.05), higher fasting plasma NEFA (P < 0.001) and higher plasma dimethylglycine (P < 0.05), compared to the TPN-CON. IUGR pigs had greater VLDL secretion, as suggested by higher microsomal transfer protein mRNA (P < 0.05). Early TPN programmed reduced lipogenesis, as indicated by lower fatty acid synthase mRNA (P < 0.05), compared to SF.ConclusionsCollectively, these findings conclude that although TPN is a lifesaving measure, feeding TPN to IUGR neonates has long-term metabolic consequences predisposing them to develop metabolic disorders in adulthood.Funding SourcesCanadian Institutes of Health Research.

Role of endogenous incretins in the regulation of postprandial lipoprotein metabolism.

Incretins are known to influence lipid metabolism in the intestine when administered as pharmacologic agents. The aggregate influence of endogenous incretins on chylomicron production and clearance is less clear, particularly in light of opposing effects of co-secreted hormones. Here, we tested the hypothesis that physiological levels of incretins may impact on production or clearances rates of chylomicrons and VLDL. A group of 22 overweight/obese men was studied to determine associations between plasma levels of glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) after a fat-rich meal and the production and clearance rates of apoB48- and apoB100-containing triglyceride-rich lipoproteins. Subjects were stratified by above- and below-median incretin response (area under the curve). Stratification yielded subgroups that differed about two-fold in incretin response. There were neither differences in apoB48 production rates in chylomicrons or VLDL fractions nor in apoB100 or triglyceride kinetics in VLDL between men with above- vs below-median incretin responses. The men with above-median GLP-1 and GLP-2 responses exhibited higher postprandial plasma and chylomicron triglyceride levels, but this could not be related to altered kinetic parameters. No differences were found between incretin response subgroups and particle clearance rates. We found no evidence for a regulatory effect of endogenous incretins on contemporaneous chylomicron or VLDL metabolism following a standardised fat-rich meal. The actions of incretins at pharmacological doses may not be reflected at physiological levels of these hormones.

Effects of dapagliflozin on postprandial lipid metabolism in type 2 diabetes mellitus.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) modulate lipid metabolism and improve cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The exact cardioprotective mechanism of SGLT2i is unclear. We evaluated the effects of SGLT2i on postprandial lipids, lipoprotein concentrations, glucose and fatty acids. A placebo-controlled randomized, proof-of-concept study. Fourteen male patients with T2DM on intensive insulin regimen were randomly and double-blind allocated to 12 weeks dapagliflozin (10 mg) or placebo. Postprandial effects were assessed with an 8-h standardized oral fat loading test. Mean glycated A1c did not change by dapagliflozin, but the mean daily insulin dose was significantly reduced. Although dapagliflozin did not affect fasting or postprandial levels of glucose and insulin, it increased the postprandial levels of glucagon. While fasting levels of free fatty acids and beta-hydroxybutyrate (bHBA) were unchanged, dapagliflozin significantly increased the postprandial bHBA response. This was seen in the context of increased postprandial glucagon levels by dapagliflozin, without influencing postprandial insulin or glucose levels. Dapagliflozin did not affect fasting or postprandial plasma cholesterol and triglycerides nor postprandial inflammatory markers. Fasting apolipoprotein B48 was decreased without affecting the postprandial response. Markers of inflammation and vascular function did not change. Treatment with dapagliflozin of patients with T2DM led to a reduction of fasting chylomicron remnants and increased postprandial ketone bodies compared to placebo suggesting enhanced hepatic fatty acid oxidation. The latter may have been caused by decreasing the insulin-glucagon ratio. The beneficial clinical effects seen in the trials using dapagliflozin most likely are not due to effects on postprandial inflammation nor postprandial lipemia.

RNA-seq reveals insights into molecular mechanisms of metabolic restoration via tryptophan supplementation in low birth weight piglet model.

Low birth weight (LBW) is associated with metabolic disorders in early life. While dietary l-tryptophan (Trp) can ameliorate postprandial plasma triglycerides (TG) disposal in LBW piglets, the genetic and biological basis underlying Trp-caused alterations in lipid metabolism is poorly understood. In this study, we collected 24 liver samples from 1-mo-old LBW and normal birth weight (NBW) piglets supplemented with different concentrations of dietary Trp (NBW with 0% Trp, N0; LBW with 0% Trp, L0; LBW with 0.4% Trp, L4; LBW with 0.8% Trp, L8; N = 6 in each group.) and conducted systematic, transcriptome-wide analysis using RNA sequencing (RNA-seq). We identified 39 differentially expressed genes (DEG) between N0 and L0, and genes within “increased dose effect” clusters based on dose-series expression profile analysis, enriched in fatty acid response of gene ontology (GO) biological process (BP). We then identified RNA-binding proteins including SRSF1, DAZAP1, PUM2, PCBP3, IGF2BP2, and IGF2BP3 significantly (P < 0.05) enriched in alternative splicing events (ASE) in comparison with L0 as control. There were significant positive and negative relationships between candidate genes from co-expression networks (including PID1, ANKRD44, RUSC1, and CYP2J34) and postprandial plasma TG concentration. Further, we determined whether these candidate hub genes were also significantly associated with metabolic and cardiovascular traits in humans via human phenome-wide association study (Phe-WAS), and analysis of mammalian orthologs suggests a functional conservation between human and pig. Our work demonstrates that transcriptomic changes during dietary Trp supplementation in LBW piglets. We detected candidate genes and related BP that may play roles on lipid metabolism restoration. These findings will help to better understand the amino acid support in LBW metabolic complications.

Significance of Postprandial Insulin and Triglycerides to Evaluate the Metabolic Response of Composite Meals Differing in Nutrient Composition – A Randomized Cross-Over Trial

Background and aimsGlucoTRIG, based on postprandial plasma insulin and triglyceride concentrations, has been recently developed as a novel index to determine the postprandial metabolic response to the meals. This study aimed to test GlucoTRIG as a measure for ranking composite meals for their metabolic effects.MethodsIn a randomized cross-over trial, healthy adult volunteers (both males and females; n = 10 for each meal) consumed three is caloric (2000 kj) test meals (meal 1, meal 2, meal 3) of varying macronutrient composition. Postmeal consumption, venous blood samples were collected to determine plasma insulin and plasma triglycerides for estimating the GlucoTRIG value using (Triglycerides180min × Insulin180min) - (Triglycerides0min × Insulin0min).ResultsThe GlucoTRIG values differed significantly (p = 0.0085) across meals. The statistical significance remains even after adjusting for confounding variables such as baseline diet, insulin, and triglycerides. The meal (M3) with a high fiber, low total fat content and containing less refined foods (fruits, beans, vegetables, plain yogurt) exhibited a significantly (p = 0.007) lower GlucoTRIG value (10 ± 7.7) compared to the other two meals, M1 (77 ± 19.8) and M2 (38 ± 12.1) which contained low processed foods, and were relatively high in fat and low in fiber meals. No statistically significant differences were observed between M1 and M2 meal.ConclusionsGlucoTRIG is a physiologically based index that may be useful to rank composite meals for reducing the risk of metabolic diseases. Further research focusing on the application of GlucoTRIG to foods, meals, and diets is warranted.ACTRN12619000973112 (Australian New Zealand Clinical Trials Registry, ANZCTR).

New targets for treating hypertriglyceridemia.

Elevated fasting and postprandial plasma triglyceride concentrations are associated with an increased risk for atherosclerotic cardiovascular disease in patients on and off low-density lipoprotein (LDL) lowering therapy. This association is not mediated by triglycerides directly. Other components of triglyceride rich lipoproteins, such as cholesterol and apolipoproteins B and -CIII can directly induce and enhance atherosclerosis. In addition, an elevated concentration of triglyceride rich lipoproteins affects the concentration, composition, function, and metabolism of LDL and high-density lipoprotein (HDL), which contributes to the risk. Especially in patients with hypertriglyceridemia, apolipoprotein B and non-HDL-cholesterol (encompassing cholesterol of all atherogenic lipoproteins) predict risk better than LDL-cholesterol and/or triglycerides. Therefore, current guidelines have stated secondary goals relating to non-HDL-cholesterol and apolipoprotein B (in addition to the primary goal relating to LDL-cholesterol). These secondary goals can be achieved by further reducing LDL-cholesterol or by decreasing triglyceride rich lipoproteins. However, only further LDL reduction has so far proven to be beneficial in outcome trials. In addition, high dose eicosapentaenoic acid (EPA) can reduce atherosclerotic cardio-vascular disease risk in patients with hypertriglyceridemia, although benefit is not (or not only) related to apolipoprotein B or non-HDL-cholesterol reduction. Non-HDL-cholesterol and apoB represent novel targets for patients with hypertriglyceridemia, but achieving LDL-cholesterol targets remains the first step for cardio-vascular risk reduction.

The zinc finger and BTB domain containing protein ZBTB20 regulates plasma triglyceride metabolism by repressing lipoprotein lipase gene transcription in hepatocytes.

Lipoprotein lipase (LPL) is responsible for the lipolytic processing of triglyceride-rich lipoproteins, the deficiency of which causes severe hypertriglyceridemia. Liver LPL expression is high in suckling rodents but relatively low at adulthood. However, the regulatory mechanism and functional significance of liver LPL expression are incompletely understood. We have established the zinc finger protein ZBTB20 as a critical factor for hepatic lipogenesis. Here, we evaluated the role of ZBTB20 in regulating liver Lpl gene transcription and plasma triglyceride metabolism. Hepatocyte-specific inactivation of ZBTB20 in mice led to a remarkable increase in LPL expression at the mRNA and protein levels in adult liver, in which LPL protein was mainly localized onto sinusoidal epithelial cells and Kupffer cells. As a result, the LPL activity in postheparin plasma was substantially increased, and postprandial plasma triglyceride clearance was significantly enhanced, whereas plasma triglyceride levels were decreased. The dysregulated liver LPL expression and low plasma triglyceride levels in ZBTB20-deficient mice were normalized by inactivating hepatic LPL expression. ZBTB20 deficiency protected the mice against high-fat diet-induced hyperlipidemia without causing excessive triglyceride accumulation in the liver. Chromatin immunoprecipitation and gel-shift assay studies revealed that ZBTB20 binds to the LPL promoter in the liver. A luciferase reporter assay revealed that ZBTB20 inhibits the transcriptional activity of LPL promoter. The regulation of LPL expression by ZBTB20 is liver-specific under physiological conditions. Liver ZBTB20 serves as a key regulator of LPL expression and plasma triglyceride metabolism and could be a therapeutic target for hypertriglyceridemia.

A Pilot Trial: Fish Oil and Metformin Effects on ApoB-Remnants and Triglycerides in Women With Polycystic Ovary Syndrome.

ContextWomen with polycystic ovary syndrome (PCOS) have increased incidence of atherogenic dyslipidemia and cardiovascular disease (CVD). Interventions targeting atherogenic dyslipidemia to reduce CVD risk are limited in women with PCOS.ObjectiveThis pilot study was conducted to determine the effect of 12 weeks of high dose fish oil (FO), metformin, and FO as an adjunct to metformin (FO-metformin) therapy on fasting and nonfasting plasma lipids and ApoB-remnants in young women with the metabolic syndrome (MetS) and PCOS.MethodsIn this open-label parallel pilot trial, women with MetS and PCOS (18-30 years of age) were randomized into 1 of 3 interventions: (1) FO; (2) metformin; and (3) FO-metformin. Plasma lipids and ApoB (48 and 100)-lipoproteins and triglycerides (TG) were measured in the fasted and postprandial state following a high-fat meal at baseline and postintervention.ResultsFO-metformin significantly lowered fasting plasma TG by >40% compared with FO and metformin treatments. Fasting plasma apoB48 was lowered 40% in FO-metformin and 15% in the FO groups from baseline to postintervention. ApoB48 area under the curve (ApoB48AUC), ApoB48 incremental AUC (ApoB48iAUC), ApoB100AUC, and ApoB100iAUC decreased in all groups from baseline to postintervention; however, these findings did not reach statistical significance.ConclusionThe findings of this pilot trial show that high dose FO and FO-metformin combination therapy tend to lower fasting and postprandial plasma TG and ApoB-lipoprotein remnants compared with metformin; however, the study is limited by small sample size. These results may be clinically significant in individuals with PCOS for management of atherogenic dyslipidemia.

1215-P: Effects of Exogenous Secretin on Postprandial Plasma Glucose and Lipids and Gallbladder Motility and Hemodynamics in Man

Secretin is best known for its effect on pancreatic exocrine secretion. It also has osmoregulatory effects and was recently identified as a potential target for the treatment of obesity. We investigated the effects of a 5-hour intravenous (iv) secretin infusion on postprandial plasma glucose and lipids and gallbladder motility as well as hemodynamics in healthy males. In a randomized, double-blind, placebo-controlled, crossover study, 25 healthy males (25.7 ± 6.1 (mean ± SD) years; BMI 23.4 ± 1.8 kg/m2) underwent two 5-hour iv infusions of secretin (1 pmol/kg/min) or placebo (saline), with an interposed 8-week washout period. After 30 minutes of infusion, a standardized liquid mixed meal was ingested. Prior to and with regular intervals during the 5-hour infusions, blood samples were drawn, ultrasonography of the gallbladder performed, and hemodynamics measured. Steady-state plasma concentrations of secretin amounted to 113 ± 2 pmol/L, i.e., ~20-fold higher than physiological levels. Postprandial plasma triglyceride excursions were higher during secretin than placebo infusions (baseline-subtracted area under curve: 111 ± 49 vs. 83 ± 36 min × pmol/L [P = 0.012]), whereas excursions in glucose, glycerol and free fatty acids were similar during placebo and secretin infusions. Compared to placebo, secretin reduced maximum gallbladder ejection fraction by 32 ± 27% (P &amp;lt;0.001) and increased mean systolic and diastolic blood pressure by 5.3 ± 4.5 (P &amp;lt;0.039) and 2.2 ± 3.2 mmHg (P &amp;lt;0.001), respectively, and increased heart rate by 5.5 ± 3.6 bpm (P &amp;lt;0.001). We conclude that a 5-hour iv infusion of secretin in healthy males has no effect on fasting and postprandial glucose levels, but reduces postprandial gallbladder contraction, while increasing plasma triglycerides, blood pressure and pulse. Disclosure M. J. Bentzen: None. S. M. Nguyen heimbürger: Speaker’s Bureau; Self; AstraZeneca. B. Hartmann: None. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. M. B. Christensen: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S.

Postprandial Lipid Metabolism in Normolipidemic Subjects and Patients with Mild to Moderate Hypertriglyceridemia: Effects of Test Meals Containing Saturated Fatty Acids, Mono-Unsaturated Fatty Acids, or Medium-Chain Fatty Acids.

Fasting and postprandial hypertriglyceridemia are causal risk factors for atherosclerosis. The prevalence of hypertriglyceridemia is approximately 25–30% and most hypertriglyceridemic patients suffer from mild to moderate hypertriglyceridemia. Data regarding dietary interventions on postprandial triglyceride metabolism of mildly to moderately hypertriglyceridemic patients is, however, sparse. In a randomized controlled trial, eight mildly hypertriglyceridemic patients and five healthy, normolipidemic controls received three separate standardized fat-meals containing either saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), or medium-chain fatty acids (MCFA) in a randomized order. Fasting and postprandial lipid parameters were determined over a 10 h period and the (incremental) area under the curve (AUC/iAUC) for plasma triglycerides and other parameters were determined. MCFA do not lead to a significant elevation of postprandial total plasma triglycerides and other triglyceride parameters, while both SFA (patients: p = 0.003, controls: p = 0.03 compared to MCFA) and MUFA (patients: p = 0.001; controls: p = 0.14 compared to MCFA) do lead to such an increase. Patients experienced a significantly more pronounced increase of plasma triglycerides than controls (SFA: patients iAUC = 1006 mg*h/dL, controls iAUC = 247 mg*h/dL, p = 0.02; MUFA: patients iAUC = 962 mg*h/dL, controls iAUC = 248 mg*h/dL, p = 0.05). Replacing SFA with MCFA may be a treatment option for mildly to moderately hypertriglyceridemic patients as it prevents postprandial hypertriglyceridemia.

Background Inactivity Blunts Metabolic Adaptations to Intense Short-Term Training.

This study determined if the level of background physical inactivity (steps per day) influences the acute and short-term adaptations to intense aerobic training. Sixteen untrained participants (23.6 ± 1.7 yr) completed intense (80%-90% V˙O2peak) short-term training (5 bouts of exercise over 9 d) while taking either 4767 ± 377 steps per day (n = 8; low step) or 16,048 ± 725 steps per day (n = 8; high step). At baseline and after 1 d of acute exercise and then after the short-term training (posttraining), resting metabolic responses to a high-fat meal (i.e., plasma triglyceride concentration and fat oxidation) were assessed during a 6-h high-fat tolerance test. In addition, responses during submaximal exercise were recorded both before and after training during 15 min of cycling (~79% of pretraining V˙O2peak). High step displayed a reduced incremental area under the curve for postprandial plasma triglyceride concentrations by 31% after acute exercise and by 27% after short-term training compared with baseline (P < 0.05). This was accompanied by increased whole-body fat oxidation (24% and 19%; P < 0.05). Furthermore, stress during submaximal exercise as reflected by heart rate, blood lactate, and deoxygenated hemoglobin were all reduced in high step (P < 0.05), indicating classic training responses. Despite completing the same training regimen, low step showed no significant improvements in postprandial fat metabolism or any markers of stress during submaximal exercise after training (P > 0.05). However, the two groups showed a similar 7% increase in V˙O2peak (P < 0.05). When completing an intense short-term exercise training program, decreasing daily background steps from 16,000 to approximately 5000 steps per day blunts some of the classic cardiometabolic adaptations to training. The blunting might be more pronounced regarding metabolic factors (i.e., fat oxidation and blood lactate concentration) compared with cardiovascular factors (i.e., V˙O2peak).

Role of Fluid Milk in Attenuating Postprandial Hyperglycemia and Hypertriglyceridemia.

Postprandial plasma glucose and triglyceride concentrations are predictive of relative cardiovascular disease (CVD) risk, and the pathogenesis of both insulin resistance and atherosclerosis has been attributed to acute states of hyperglycemia and hypertriglyceridemia. Postprandial lipemia and hyperglycemia suppress vascular reactivity and induce endothelial dysfunction. Epidemiological studies suggest that chronically-high consumption of milk and milk products is associated with a reduced risk of type 2 diabetes, metabolic syndrome, and CVD. The addition of dairy products to meals high in carbohydrates and fat may lessen these risks through reductions in postprandial glucose and triglyceride responses. Purported mechanisms include dairy proteins and bioactive compounds, which may explain the inverse relationship between dairy consumption and cardiometabolic diseases. The current review evaluates the available literature describing the relationships between metabolic dysfunction, postprandial metabolism, and vascular dysfunction and discusses the potential role of milk and dairy products in attenuating these impairments.

Daily Step Count and Postprandial Fat Metabolism.

Two benefits of acute exercise are the next day's lowering of the postprandial plasma triglyceride response to a high-fat meal and increased fat oxidation. However, if activity levels (daily steps) are very low, these acute adaptations to exercise do not occur. This phenomenon has been termed "exercise resistance." This study sought to systematically reduce daily step number and identify the range of step counts that elicit "exercise resistance." Ten participants completed three, 5-d trials in a randomized, crossover design with differing levels of step reduction. After 2 d of controlled activity, participants completed 2 d of LOW, LIMITED, or NORMAL steps (2675 ± 314, 4759 ± 276, and 8481 ± 581 steps per day, respectively). Participants completed a 1-h bout of running on the evening of the second day. High-fat tolerance tests were performed on the next morning, and postprandial responses were compared. After LOW and LIMITED, postprandial incremental area under the curve (AUC) of plasma triglyceride was elevated 22%-23% compared with NORMAL (P < 0.05). Whole body fat oxidation was also significantly lower (16%-19%, P < 0.05, respectively) in LOW and LIMITED compared with NORMAL. No significant differences were found between LOW and LIMITED. Two days of step reduction to approximately 2500-5000 steps per day in young healthy individuals impairs the ability of an acute bout of exercise to increase fat oxidation and attenuate postprandial increases in plasma triglycerides. This suggests that "exercise resistance" occurs in individuals taking approximately 5000 or fewer steps per day, whereas 8500 steps per day protects against exercise resistance in fat metabolism. It seems that fat metabolism is influenced more by the inhibitory effects of inactivity than by the stimulating effects derived from 1 h of moderate-intensity running.

Postprandial Apolipoprotein B48 is Associated with Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis.

Objective: To describe postprandial lipemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis measured as carotid intima-media thickness (cIMT). Methods: We performed an observational study of 40 patients with RA and 40 sex and age-matched controls. Patients with dyslipidemia were excluded. Pathologically increased cIMT was defined as a carotid thickness greater than the 90th percentile (>p90) for age and sex. Fasting and postprandial plasma lipids, cholesterol, triglycerides, apolipoprotein B48 (ApoB48), and total ApoB were evaluated. The other variables included were clinical and laboratory values, Framingham score, and the 28-joint Disease Activity Score (DAS28). Two multivariate models were constructed to identify factors associated with pathologic cIMT in patients with RA. Results: Fasting lipid values were similar in patients with RA and controls, although those of postprandial ApoB48 were higher (median (IQR), 14.4 (10.8–12.1) vs. 12.1 (2.3–9,8); p = 0.042). Pathologic cIMT was recorded in 10 patients with RA (25%) and nine controls (22.5%). In patients with RA, pathologic cIMT was associated with postprandial ApoB48 (OR (95% CI), 1.15 (1.0–1.3)) and total ApoB (OR [95% CI], 1.12 [1.1–1.2]). The second model revealed a mean increase of 0.256 mm for cIMT in patients with elevated anticitrullinated protein antibodies (ACPAs). Conclusion: Postprandial ApoB48 levels in patients with RA are higher than in controls. Postprandial ApoB48 and total ApoB levels and markers of severity, such as ACPAs, are associated with pathologic cIMT in patients with RA. Our findings could indicate that these atherogenic particles have a negative effect on the endothelium.