Postprandial High-density Lipoprotein Cholesterol Research Articles

Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels

Dyslipidemia is a main driver of cardiovascular diseases. The ability of macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism is key to the development of new treatments. Here, we investigated how adipose tissue macrophages regulate post-prandial cholesterol transport. Single-cell RNA sequencing and protected bone marrow chimeras demonstrated that ingestion of lipids led to specific transcriptional activation of a population of resident macrophages expressing Lyve1, Tim4, and ABCA1. Blocking the phosphatidylserine receptor Tim4 inhibited lysosomal activation and the release of post-prandial high density lipoprotein cholesterol following a high fat meal. Both effects were recapitulated by chloroquine, an inhibitor of lysosomal function. Moreover, clodronate-mediated cell-depletion implicated Tim4+ resident adipose tissue macrophages in this process. Thus, these data indicate that Tim4 is a key regulator of post-prandial cholesterol transport and adipose tissue macrophage function and may represent a novel pathway to treat dyslipidemia.

Effects of Acute Cocoa Supplementation on Postprandial Apolipoproteins, Lipoprotein Subclasses, and Inflammatory Biomarkers in Adults with Type 2 Diabetes after a High-Fat Meal.

Dyslipidemia and inflammation exacerbate postprandial metabolic stress in people with diabetes. Acute dietary supplementation with polyphenols shows promise in improving postprandial metabolic stress in type 2 diabetes (T2D). Cocoa is a rich source of dietary polyphenols with demonstrated cardioprotective effects in adults without diabetes. To date, the acute effects of cocoa on postprandial lipids and inflammation have received little attention in the presence of T2D. This report expands on our earlier observation that polyphenol-rich cocoa, given as a beverage with a fast-food-style, high-fat breakfast, increased postprandial high-density lipoprotein-cholesterol (HDL-C) in adults with T2D. We now test whether polyphenol-rich cocoa modulated postprandial apolipoproteins (Apo-A1, B), non-esterified fatty acids, nuclear magnetic resonance (NMR)-derived lipoprotein subclass profiles, and select biomarkers of inflammation following the same dietary challenge. We found that cocoa decreased NMR-derived concentrations of total very low-density lipoprotein and chylomicron particles and increased the concentration of total HDL particles over the 6-hour postprandial phase. Serum interleukin-18 was decreased by cocoa vs. placebo. Thus, polyphenol-rich cocoa may alleviate postprandial dyslipidemia and inflammation following a high-fat dietary challenge in adults with T2D. The study was registered at clinicaltrials.gov as NCT01886989.

Postprandial Paraoxonase 1 Activity Following Consumption of Recommended Amounts of Mixed Meals in Healthy Males.

Postprandial lipid level increases induce oxidative stress, which is involved in atherogenesis. The antioxidant properties of paraoxonase 1 (PON1) have attracted attention. However, changes in postprandial PON1 levels differ across prior studies, and changes in PON1 lactonase activity, potentially relevant to PON1 physiology, after the consumption of ordinary meals are unknown. Herein we evaluated postprandial serum lipid levels and PON1 changes following mixed-meal consumption of the amounts recommended for ordinary meals. Nine healthy male volunteers consumed three different meals in a randomized cross-over design. The test meals were as follows: S, white rice; SMF, S with fat-containing protein-rich main dishes; and SMFV: SMF with vegetable dishes. The serum lipid concentrations and PON1 lactonase and arylesterase activities were determined during a three-hour period after the consumption of these meals. The postprandial triglyceride levels were higher after consuming the SMF and SMFV meals than after consuming the S meal. Despite postprandial high-density lipoprotein cholesterol being unchanged, PON1 lactonase activity was decreased, while PON1 arylesterase activity was increased in the postprandial state after all test meals. Postprandial changes in lactonase and arylesterase activities did not differ among the test meals. Inverse changes in PON1 lactonase and arylesterase activities were observed after consuming recommended ordinary meals. This observation provides useful information for choosing PON1 species as postprandial markers.

Impact of corpulence parameters and haemoglobin A1c on metabolic control in type 2 diabetic patients: comparison of apolipoprotein B/A-I ratio with fasting and postprandial conventional lipid ratios

Background and objectiveThe incidence of diabetes co-morbidities could probably be better assessed by studying its associations with major corpulence parameters and glycaemic control indicators. We assessed the utility of body mass index (BMI), waist circumference (WC), and glycosylated haemoglobin (HbA1c) levels in metabolic control for type 2 diabetic patients.MethodsFasting and postprandial blood samples were collected from 238 type 2 diabetic patients aged 57.4±11.9 years. The sera were analysed for glucose, HbA1c, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and apolipoproteins (apoA-I and apoB). Ratios of lipids and apolipoproteins were calculated and their associations with BMI, WC, and HbA1c levels were analysed.ResultsOur investigation showed increases in most fasting and postprandial lipid parameters according to BMI and WC. In men, postprandial HDL-c and TG levels were significantly higher (p<0.05) in overweight and obese patients, respectively, as well as in patients with abdominal obesity. Contrariwise, postprandial TC levels were significantly higher (p<0.01) in overweight and abdominal obese women. However, elevations of apoA-I and apoB levels were according to BMI and WC in both genders. There was a strong influence of BMI, WC, and HbA1c levels on the apoB/apoA-I ratio compared to traditional fasting and postprandial lipid ratios in both men and women. The apoB/apoA-I ratio was more correlated with postprandial TC/HDL and LDL-c/HDL-c ratios in men and with postprandial TG/HDL-c in women.ConclusionThe apoB/apoA-I ratio is helpful in assessing metabolic risk caused by overall obesity, abdominal obesity and impaired glycaemia in type 2 diabetic patients.

Effects of nateglinide and acarbose on glycemic excursions in standardized carbohydrate and mixed-meal tests in drug-naïve type 2 diabetic patients

The aim of this study was to compare the effects of nateglinide and acarbose on glycemic excursions and postprandial glucose profiles with different types of meals (standardized carbohydrate and mixed meals) in drug-naïve type 2 diabetic patients. A randomized, parallel-group prospective design clinical trial was conducted and a total of 39 drug-naïve patients (16 males and 23 females, aged 56.7±10.2 years) were enrolled. The patients were randomly divided into group A [nateglinide 120 mg three times daily (t.i.d.), n=19] and group B (acarbose 50 mg t.i.d., n=20). The standardized carbohydrate and mixed-meal tests were performed at baseline and at the end of study. Continuous glucose monitoring system (CGMS) data were recorded. Various parameters that measure glucose variability were derived from the CGMS data. In the standardized carbohydrate meal tests, the postprandial glucose excursions (PPGEs) were significantly decreased in the two groups after 12 weeks of treatment (P<0.05), whereas the decrease was more prominent in the acarbose compared to the nateglinide group (P=0.138). In the mixed-meal tests, the mean sensor glucose values [24-h mean blood glucose (MBG)] were significantly decreased in the two groups after 12 weeks of treatment (P<0.05) and the parameters of glucose excursions, including standardized deviation (SD), largest amplitude of glycemic excursion (LAGE), mean of daily differences (MODD) and mean amplitude of glycemic excursion (MAGE), were reduced in the two groups. However, the decreases in SD and LAGE in the nateglinide group were statistically significant, whereas in the acarbose group only the decreases in LAGE were statistically significant. The efficiency of nateglinide or acarbose in lowering postprandial 120-min hyperglycemia were similar in the standardized carbohydrate meal test. However, acarbose was more efficient in lowering postprandial 30- and 60-min hyperglycemia (P<0.05) compared to nateglinide. The fasting and postprandial total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) had a tendency to decrease from the baseline after 12 weeks of treatment with nateglinide, whereas fasting and postprandial high-density lipoprotein cholesterol (HDL-C) had a tendency to increase. Acarbose did not affect the fasting or postprandial lipid profiles after 12 weeks of treatment (P>0.05). In conclusion, nateglinide and acarbose effectively improved postprandial glycemic control, although acarbose was shown to be more efficient in controlling early (30 and 60 min) postprandial glucose excursions in the carbohydrate meal test, whereas nateglinide was shown to be superior to acarbose in controlling postprandial glucose excursions in the mixed-meal test.

Differential Effects of α-Glucosidase Inhibitors on Postprandial Plasma Glucose and Lipid Profile in Patients with Type 2 Diabetes Under Control with Insulin Lispro Mix 50/50

The additive effect of α-glucosidase inhibitors (α-GIs) was investigated in patients with type 2 diabetes (T2D) under control with rapid-acting insulin analog. Thirty-six poorly controlled T2D patients were recruited, and plasma glucose (PG) was controlled by three times daily injection of insulin lispro mix 50/50 (Mix50) to maintain fasting PG <130 mg/dL and 2-h postprandial PG (PPG) <180 mg/dL. Another group of 20 patients was randomly assigned to either 0.3 mg of voglibose or 50 mg of miglitol, which was administered at breakfast every other day. Another group of 16 patients was assigned to a crossover study, in which each α-GI was switched every day during the 6-day study. PPG, C-peptide, and lipid profile were analyzed. The addition of voglibose had no effect on PPG, but miglitol blunted the PPG rise and significantly decreased 1-h and 2-h postprandial C-peptide levels compared with Mix50 alone. In addition, miglitol significantly decreased the 1-h postprandial triglyceride rise and the remnant-like particle-cholesterol rise, while it increased the 1-h postprandial high-density lipoprotein-cholesterol and apolipoprotein A-I levels in the crossover study. Miglitol appears to have rapid action, which appears earlier than that of lispro. The combination of miglitol and Mix50 seems effective for the control of PPG and lipid profile in T2D.

Post-prandial lipid levels for assessing target goal achievement in type 2 diabetic patients taking statin.

It is inconvenient to perform serum lipid analysis in fasting state in diabetic patients with drug treatment. In patients with statin treatment and Asian diet, it has not been clearly known whether non-fasting values could be used for the clinical decision making in diabetic patients. In this study, fasting and post-prandial plasma lipid profiles of hospitalized type 2 diabetic patients taking statin, were measured in whom standard diabetic breakfast in traditional Korean style were provided. In repeated-measures ANOVA, there were no significant differences among fasting, post-prandial 2 and 4 hr low-density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol values. When compared to fasting levels, both post-prandial 2 hr and 4 hr LDL cholesterol levels were misclassified as not achieved target goal only in 4% of patients. Post-prandial HDL cholesterol matched with fasting values in women, without exception. In conclusion, the fasting and post-prandial LDL and HDL cholesterol levels are not significantly different each other and can be used in the assessment of achieving target goal in type 2 diabetes taking statin after Korean diet.

Lipoprotein metabolism mediates the association of MTP polymorphism with β-cell dysfunction in healthy subjects and in nondiabetic normolipidemic patients with nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) predicts incident diabetes independently of insulin resistance, adiposity and metabolic syndrome through unclear mechanisms. Dietary fat consumption and lipoperoxidative stress predispose to diabetes in the general population and to liver injury in NASH. Microsomal triglyceride transfer protein (MTP) polymorphism modulates lipoprotein metabolism in the general population and liver disease in NASH; a functional MTP polymorphism recently predicted incident diabetes independently of insulin resistance in the general population. We simultaneously assessed the impact of MTP polymorphism, diet, adipokines and lipoprotein metabolism, on glucose homeostasis in NASH. MTP −493G/T polymorphism, dietary habits, adipokines and postprandial triglyceride-rich lipoproteins, high-density lipoprotein cholesterol (HDL-C) and oxidized low-density lipoprotein (oxLDL) responses to an oral fat load, were cross-sectionally correlated to oral glucose tolerance test- and frequently sampled intravenous glucose tolerance test-derived Minimal Model indexes of glucose homeostasis in 40 nondiabetic normolipidemic patients with NASH and 40 age-,sex- and body mass index-matched healthy controls. Despite comparable insulin resistance, fasting lipids, adipokines and dietary habits, MTP GG genotype had significantly more severe β-cell dysfunction; higher plasma Tg, FFA, intestinal and hepatic very low-density lipoprotein 1 subfractions and oxLDL responses and deeper HDL-C fall than GT/TT carriers in patients and controls. Postprandial HDL-C and oxLDL responses independently predicted β-cell dysfunction and mediated the effect of MTP polymorphism on β-cell function. In nondiabetic normolipidemic NASH, MTP −493G/T polymorphism modulates β-cell function, an effect mediated by postprandial HDL-C and oxLDL metabolism. The impact of this polymorphism on the risk of diabetes and the efficacy of lipid-lowering therapies in restoring β-cell function in NASH, even with normal fasting lipid values, warrant further investigation.

Influence of acute exercise with and without carbohydrate replacement on postprandial lipid metabolism

Acute exercise, undertaken on the day before an oral fat tolerance test (OFTT), typically reduces postprandial triglycerides (TG) and increases high-density lipoprotein-cholesterol (HDL-C). However, the benefits of acute exercise may be overstated when studies do not account for compensatory changes in dietary intake. The objective of this study was to determine the influence of acute exercise, with and without carbohydrate (CHO) replacement, on postprandial lipid metabolism. Eight recreationally active young men underwent an OFTT on the morning after three experimental conditions: no exercise [control (Con)], prolonged exercise without CHO replacement (Ex-Def) and prolonged exercise with CHO replacement to restore CHO and energy balance (Ex-Bal). The exercise session in Ex-Def and Ex-Bal consisted of 90 min cycle ergometry at 70% peak oxygen uptake (Vo(2peak)) followed by 10 maximal 1-min sprints. CHO replacement was achieved using glucose solutions consumed at 0, 2, and 4 h postexercise. Muscle glycogen was 40 +/- 4% (P < 0.05) and 94 +/- 3% (P = 0.24) of Con values on the morning of the Ex-Def and Ex-Bal OFTT, respectively. Postprandial TG were 40 +/- 14% lower and postprandial HDL-C, free fatty acids, and 3-hydroxybutyrate were higher in Ex-Def compared with Con (P < 0.05). Most importantly, these exercise effects were not evident in Ex-Bal. Postprandial insulin and glucose and the homeostatic model assessment of insulin resistance (HOMA(IR)) were not significantly different across trials. There was no relation between the changes in postprandial TG and muscle glycogen across trials. In conclusion, the influence of acute exhaustive exercise on postprandial lipid metabolism is largely dependent on the associated CHO and energy deficit.

Lipid‐lowering therapy does not affect the postprandial drop in high density lipoprotein‐cholesterol (HDL‐c) plasma levels in obese men with metabolic syndrome: a randomized double blind crossover trial

The postprandial lipid metabolism in metabolic syndrome patients is disturbed and may add to the increased cardiovascular risk in these patients. It is not known whether postprandial high density lipoprotein-cholesterol (HDL-c) metabolism is also affected and whether this can be influenced by statin and/or ezetimibe treatment. Prospective, randomized, double blind, crossover trial comparing simvastatin 80 mg with simvastatin/ezetimibe 10 mg/10 mg treatment for 6 weeks on postprandial HDL-c metabolism in 15, nonsmoking, male, obese metabolic syndrome patients (Adult Treatment Panel III, ATPIII). Only study medication was allowed. HDL-c concentrations, cholesteryl ester transfer (CET), CET protein (CETP) mass and adiponectin were measured before and after oral fat loading. ClinicalTrials.gov NCT00189085. Plasma HDL-c levels remained stable during continuous fasting following an overnight fast. Pre-fat load HDL-c concentrations without treatment, after simvastatin and simvastatin/ezetimibe treatment were 1.15 +/- 0.04, 1.16 +/- 0.05 and 1.11 +/- 0.04 mmol/l. Fat load induced a 11% drop in HDL-c plasma levels; 1.02 +/- 0.05 mmol/l (P < 0.001) which was not affected by either therapy. Triglyceride levels during fat load were similar after both treatments. Total CET increased from 9.73 +/- 0.70 to 12.20 +/- 0.67 nmol/ml/h (P = 0.004). Four hours after fat loading CETP mass was increased while adiponectin levels were decreased, irrespective of treatment. HDL-c levels decrease as CET increases after fat loading in obese metabolic syndrome patients. This is not influenced by either simvastatin or simvastatin/ezetimibe treatment. After fat loading, CETP mass and CET increased, and adiponectin decreased pointing towards a potential role for intra-abdominal fat. Decreased postprandial HDL-c levels may contribute to the increased cardiovascular risk in metabolic syndrome patients on top of already low HDL-c levels.

Estimating the fasting triglyceride concentration from the postprandial HDL-cholesterol and apolipoprotein CIII concentrations

Hypertriglyceridemia is an important risk factor for atherosclerosis. In the fasting state, the triglyceride (TG) concentration is correlated significantly with the high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein CIII (apoCIII) concentrations. A postprandial change is evident in TG, but negligible in HDL-C and apoCIII. We investigated whether the fasting TG concentration could be estimated from the postprandial HDL-C and apoCIII concentrations. We measured the TG, HDL-C, and apoCIII concentrations at seven points a day in 58 inpatients. Multiple regression analysis showed that the actual fasting TG concentration was strongly correlated with the TG concentration estimated from the fasting HDL-C and apoCIII concentrations (ln[TG] fasting = 0.0140[apoCIII] fasting − 0.724[HDL-C] fasting − 0.142, r = 0.852, p < 0.001). This equation was also fit to the fasting data from 163 outpatients ( r = 0.883, p < 0.001). Although the TG concentration increased by up to 28.2%, the HDL-C and apoCIII concentrations changed little during the day. When we substituted the postprandial HDL-C and apoCIII concentrations for the respective fasting values in this equation, there were still strong positive correlations ( r = 0.794–0.840) between the actual and estimated fasting TG concentrations throughout the day. In conclusion, the fasting TG concentration can be estimated from the postprandial HDL-C and apoCIII concentrations.

Postprandial triglyceride response in patients with polycystic ovary syndrome: relationship with waist-to-hip ratio and insulin

Objective: To examine the postprandial triglyceride response to a high-fat meal in women with polycystic ovary syndrome (PCOS) compared with a matched control group. Design: Controlled clinical study. Setting: Department of Endocrinology and Pathophysiology, School of Medicine, Universidad de Los Andes. Patient(s): 18 Hispanic women with PCOS (nine overweight and nine nonobese) and 9 healthy control women. Intervention(s): Biometric measures and blood sample collection. Main Outcome Measure(s): Insulin and glucose levels during a standard oral glucose tolerance test. Plasma triglyceride, cholesterol, and high-density lipoprotein cholesterol levels were measured at baseline and at 4, 5, and 6 h after a high-fat meal. Result(s): Both obese and nonobese PCOS women had higher waist-to-hip ratios than controls. PCOS women had higher levels of fasting and postglucose insulin and fasting triglyceride and postprandial triglyceride response and had lower levels of postprandial high-density lipoprotein cholesterol response, but no significant differences within PCOS groups were observed. Conclusion(s): An expanded postprandial hypertriglyceridemia in PCOS women is related to a higher waist-to-hip ratio and insulin resistance, regardless of obesity, and contributes to increase the risk for coronary artery disease.

Postprandial reduction in high-density lipoprotein cholesterol concentrations in postmenopausal women: Improvement by 17β-estradiol

The aim of the study was to characterize postprandial high-density lipoprotein (HDL) cholesterol metabolism in postmenopausal women and to evaluate the effect of replacement therapy with 17β-estradiol. Sixteen healthy normolipidemic (plasma cholesterol, 5.39 ± 0.68 mmol/L; plasma triglycerides [TGs], 1.24 ± 0.55 mmol/L) postmenopausal women received an oral vitamin A fat tolerance test (50 g fat with 60,000 IU vitamin A/m 2 body surface area). Venous blood samples were taken before the test, at hourly intervals up to 8 hours, and 24 hours after ingestion of the fat load for determination of HDL cholesterol, HDL TG, and HDL apolipoprotein (apo) A-I concentrations. TG and vitamin A concentrations were also measured. A subgroup of six women were treated with 2 mg micronized 17β-estradiol orally each day for 6 weeks, after which the oral vitamin A fat tolerance test was repeated. A reduction in plasma HDL cholesterol concentrations was observed 3 to 8 hours after ingestion of the fat load, and the minimal postprandial HDL cholesterol concentration was, on average, 31.7% ( P = .04) lower than the fasting HDL cholesterol concentration. HDL cholesterol had returned to the initial value 24 hours after the fat load. The decrease in postprandial HDL cholesterol concentrations was attenuated by treatment with 17β-estradiol. The area under the curve (AUC) for the postprandial reduction in HDL cholesterol improved substantially by 66% during 17β-estradiol (−2.4 ± 2.6 mmol · h · L −1 before 17β-estradiol and −1.1 ± 1.2 mmol · h · L −1 during 17β-estradiol, P = .038). In conclusion, HDL cholesterol concentrations decreased by 32% in the postprandial state in normolipidemic postmenopausal women, indicating that HDL cholesterol must be measured in the fasting state. Replacement therapy with 17β-estradiol reduced the postprandial decrease in HDL cholesterol by 66%. This effect of 17β-estradiol can be beneficial in reducing the risk of coronary artery disease.