Postprandial Hyperlipidemia: Its Pathophysiology, Diagnosis, Atherogenesis, and Treatments.

Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide 1 analogues have been shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments. However, there are some problems with the diagnosis for postprandial hyperlipidemia. Postprandial hyperlipidemia cannot be specifically defined by measures such as TG levels 2 h after a meal. To study interventions for postprandial hyperlipidemia with the outcome of preventing the onset of ASCVD, it is necessary to define postprandial hyperlipidemia using reference values such as IGT.

A New Case of Abetalipoproteinemia Caused by Novel Compound Heterozygote Mutations in the MTTP Gene without Fat or Vitamin Malabsorption.

Abetalipoproteinemia (ABL) is a rare disease characterized by extremely low apolipoprotein B (apoB)-containing lipoprotein levels, dietary fat, and fat-soluble vitamin malabsorption, leading to gastrointestinal, neuromuscular, and ophthalmological symptoms. We herein report a case of ABL with novel compound heterozygous mutations in the microsomal triglyceride transfer protein gene (c.1686_1687del [p.Ser563TyrfsTer10] and c.1862T>C [p.Ile621Thr]), identified via panel sequencing. Although the patient had extremely reduced low-density lipoprotein cholesterol levels and a fatty liver, he did not exhibit other typical complications. Furthermore, unlike typical ABL, this patient had a preserved apoB-48 secretion and increased concentrations of high-density lipoprotein cholesterol, which may account for the normal serum fat-soluble vitamin levels.

Apo B-48 gene expression and low-density lipoprotein as a factor for increased insulin resistance and severity of acne.

BACKGROUND: The contribution of insulin to acne is that it stimulates the synthesis of androgenic hormones, which are important in the development of excess sebum, hyperkeratinization, and sebaceous gland cell growth. OBJECTIVE: To ascertain whether the lipid profile abnomalies seen in acne vulgaris are genetically induced, we also seek to establish a link between insulin resistance and lipid profiles. METHODS: An analytical cross-sectional study with case-control design research investigation of 72 individuals with acne vulgaris and 72 healthy volunteers was carried out. Both groups' medical histories were taken, as were the severity and duration of the disease among acne sufferers, as well as demographic data. Anthropometry tests were performed on both groups, including their weights, height, and circumference of waist, as well as the profile of lipids, blood glucose levels after a fast, insulin levels during fasting, resistance to insulin, and Apo B-48 folding change. RESULTS: Severe acne vulgaris patients showed significantly increased TG, TC, LDL-C, blood glucose levels after a fast, fasting insulin, and resistance to insulin levels. P = 0.005 showed that Apo B-48 expression increased in patients compared to healthy people. Apo B-48 folding change and insulin resistance were found to have a substantial positive simple linear association. Acne vulgaris, whether mild, moderate, or severe, has a significant positive linear connection with insulin resistance. CONCLUSION: Acne patients had an abnormal in lipid profile. Acne individuals with severe form are more inclined to acquire resistance to insulin as well as higher glucose and insulin levels. Apo B-48 gene expression is elevated in acne individuals with severe form who have lipid abnormalities. This illustrating the importance of genetic variables in acne, insulin resistance, lipid profile modifications as well as Isotretinoin, a standard acne medication, can also cause lipid irregularities.

Evaluation of circulating miR-122, miR-30c and miR-33a levels and their association with lipids, lipoproteins in postprandial lipemia.

AIMS: Postprandial lipemia is characterized by an increase in triglyceride-rich lipoproteins after fatty meals. MicroRNAs (miRs) play important roles in lipid and lipoprotein metabolism. The aim of this study was to determine relationship between levels of plasma miR expression and lipoprotein metabolism-related proteins in subjects with normal (NPR) and high postprandial response (HPR) in postprandial period. MATERIALS AND METHODS: The oral fat tolerance test was applied to 22 individuals with NPR and 22 with HPR. KEY FINDINGS: Increased expressions of miR-122 and miR-33a and miR-122/30c ratio and decreased miR-30c expression were observed in fasting and postprandial period of HPR compared with NPR. ROC curve analysis showed that miR-122/30c ratio is a good biomarker for postprandial lipemia (AUC: 0.97, p < 0.001). Levels of TG, MTTP, and Apo B-48 and chylomicron (CM) particle size were significantly higher in HPR than in NPR (p < 0.05). The miR-122/30c ratio at 2 h was positively correlated with CM particle size, and with TG, MTTP and Apo B-48 levels at 4th hour. miR-33a expression decreased in HPR and was negatively correlated with ABCA1 and Apo A-1 levels at 4th hour of the postprandial period in both groups. SIGNIFICANCE: Increased miR-122 and decreased miR-30c expression levels in HPR may play critical roles in elevated or prolonged postprandial lipemia. The miR122/30c ratio exhibited good association with MTTP, Apo B-48 and TG levels, and with CM particle size, and may be a reliable marker for evaluating postprandial lipemia. miR-33a may also play a key role in decreased HDL-C in postprandial lipemia.

Correlates of pentraxin 3 serum concentration in men and women with type 2 diabetes.

Elevated levels of plasma pentraxin 3 (PTX3), a marker of inflammation, are associated with the risk of developing cardiovascular diseases in the general population, as well as in patients with type 2 diabetes (DM2). In this study, we aimed to determine factors associated with PTX3 serum concentrations in men and women with DM2. The study included 116 consecutive patients (67 men and 49 women) with DM2 from an outpatient diabetic clinic. Men were characterised by lower age and higher uric acid, creatinine and bilirubin concentrations and waist/hip ratio than women. In women, low-density lipoprotein cholesterol (LDL-C) levels were higher than in men. In men, median (interquartile range) values of PTX3 concentration were 4.02 (1.99), and in women they were 4.53 (3.31) ng/ml (NS). In men, PTX3 concentrations correlated with total cholesterol (TC), triglycerides, apolipoprotein (Apo) C3, Apo B48, Glc and creatinine levels. In women, PTX3 correlated significantly with TC and LDL-C and Apo B100. Partial regression analysis revealed that after adjusting for age, PTX3 concentrations in men were significantly associated with TC, LDL-C, triglycerides, creatinine, Apo C3 and Apo B48, while in women they were associated with TC, LDL-C and Apo B100. The results could be of importance in sex-specific prevention of vascular complications in DM2 patients.

Identification of Apo B48 and other novel biomarkers in amyotrophic lateral sclerosis patient fibroblasts.

AIM: Amyotrophic lateral sclerosis (ALS) is a debilitating fatal neurodegenerative disorder. 90-95% of ALS cases are sporadic with no clear risk factors associated with the disease. Identification of biomarkers associated with ALS may lead to early detection and make it more amenable to therapeutic intervention. MATERIALS & METHODS: SILAC was used to quantitatively analyze the proteomes of ALS and control human fibroblasts. RESULTS: Out of total of 861 proteins identified, 33 were found to be differentially regulated. ApoB48 and Hsp20 were downregulated, while Fibulin-1 was upregulated. CONCLUSION: We report the differential regulation of these proteins in ALS fibroblasts, and their potential as novel biomarkers and possible drug targets for ALS.

Consumption of low doses of fat prevents the postprandial rise in chylomicron particle concentration and remnant accumulation in healthy normolipidaemic males.

Chylomicron particles are continually synthesised and secreted from the intestine even in the absence of ingested fat. It is possible that following consumption of low doses of fat the basal level of chylomicron secretion and subsequent metabolism are sufficient to metabolise this fat without an increase in postprandial chylomicron concentrations. To test this hypothesis, healthy male subjects were randomised to receive, on three separate occasions, meals containing a range of doses of fat (average 8·1-19 g) and effects on postprandial lipaemia and chylomicron concentration were determined. Furthermore, to delineate the effect on lipid-rich v. lipid-poor (remnant) forms lipid levels were also determined in a density <1·006 g/ml fraction. Following consumption of the very low dose of fat the postprandial concentration of chylomicrons was unaltered, whereas following the medium dose postprandial chylomicron concentrations were significantly increased. Interestingly, this increase was only detected in the lipid-rich chylomicron fraction, with postprandial levels of chylomicron remnants remaining unchanged. In conclusion, it appears that consumption of what would be considered low to medium doses of fat are not associated with transient postprandial increases in chylomicron remnants in healthy male subjects.