Hypertriglyceridemia In Individuals Research Articles

Dissociation between liver fat content and fasting metabolic markers of selective hepatic insulin resistance in humans.

Fasting hyperglycemia and hypertriglyceridemia are characteristic of insulin resistance (IR) and rodent work has suggested this may be due to selective hepatic IR, defined by increased hepatic gluconeogenesis and de novo lipogenesis (DNL), but this has not been shown in humans. Cross-sectional study in men and women across a range of adiposity. Medication-free participants (n = 177) were classified as normoinsulinemic (NI) or hyperinsulinemic (HI) and as having low (LF) or high (HF) liver fat content measured by magnetic resonance spectroscopy. Fractional gluconeogenesis (frGNG) and hepatic DNL were measured using stable isotope tracer methodology following an overnight fast. Although HI and HF groups had higher fasting plasma glucose and triglyceride concentrations when compared to NI and LF groups respectively, there was no difference in frGNG. However, HF participants tended to have lower frGNG than LF participants. HI participants had higher DNL compared to NI participants but there was no difference observed between liver fat groups. Taken together, we found no metabolic signature of selective hepatic IR in fasting humans. DNL may contribute to hypertriglyceridemia in individuals with HI but not those with HF. Glycogenolysis and systemic glucose clearance may have a larger contribution to fasting hyperglycemia than gluconeogenesis, especially in those with HF, and these pathways should be considered for therapeutic targeting.

Association of TCF7L2 Variants in Type 2 Diabetes Mellitus with Hypertriglyceridemia - A Case-Control Study.

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic condition involving various genetic and environmental factors leading to impaired insulin secretion, resulting in hyperglycemia. The transcription factor 7-like 2 (TCF7L2) gene is an element of the Wnt signaling pathway that plays an important role in glucose and lipid metabolism. The aim of this study is to evaluate the association of TCF7L2 rs7903146 and rs12255372 polymorphisms in T2DM with hypertriglyceridemia. We investigated the effect of rs7903146 and rs12255372 on T2DM with high triglyceride (TG) levels in 60 patients and 20 controls. The anthropometric measurements and biochemical tests were assessed. Peripheral blood samples were collected, and genomic DNA was extracted. The genotyping of TCF7L2 polymorphisms was carried out using polymerase chain reaction (PCR)-based direct sequencing and allele-specific PCR methods. The T2DM patients and controls were compared by means of the t-test, Chi-square test, odds ratio (OR), and 95% confidence interval (CI) using Epi Info v7. The HbA1c was found to be 9.7 ± 2.1 and 5.4 ± 0.5% in patients and controls, respectively. The average TG levels (P < 0.005) in patients were 205.2 ± 145.7 and 106.4 ± 27.4mg/dl in controls. Significant evidence of association was found in T2DM patients having high TG levels with rs7903146 CT/TT (OR: 4.89; P = 0.0105) and rs12255372 GT/TT (OR: 5.23; P = 0.0101) genotypes when compared to controls. The results of this study show that TCF7L2 rs7903146 CT/TT and rs12255372 GT/TT genotypes are significantly associated with the risk of hypertriglyceridemia in individuals with T2DM among the studied population.

Impact of hypertension, overweight, hypertriglyceridemia and their combination for mortality rate according to the results of a 27-year cohort prospective study

To study influence of hypertension, overweight, hypertriglyceridemia and their combinations for all-cause and cardiovascular mortality risk formation.Methods.The prevalence of hypertension, overweight and hypertriglyceridemia was studied (1988-1991) by 27-year prospective cohort study of unorganized population of Tomsk (1546 persons - 916 female and 630 male). The predictive value of these risk factors for all-cause and cardiovascular mortality risk formation were researched in 2015. Hypertension was diagnosed in persons with blood pressure greater or equal to 140/90 mm Hg, overweight was diagnosed in people with body mass index 25 kg/m2, hypertriglyceridemia was diagnosed in individuals having high blood level of triglycerides (greater or equal to 1.7).Results. Influence of hypertension for all-cause (relative risk (RR) 2.2) and cardiovascular mortality (RR 3.38) risk formation was detected. A hypertension related elevation of mortality risk was observed both among women and men and in all age groups with the exception of men 40-59 years (the results for cardiovascular mortality in these persons was statistically insignificant). We established that hypertension had the independent significant contribution for mortality risk formation. It is shown that RR of all-cause mortality 1.25 times (cardiovascular mortality 1.8 times) more in overweight persons. Increase of relative mortality risk was detected in overweight women, especially in women 20-39 years old. Hypertriglyceridemia increases relative risk of all-cause mortality 1.46 times, relative risk of cardiovascular mortality 2.15 times, especially in individuals 40-59 years old. It was revealed that hypertriglyceridemia is significant risk factor for all-cause mortality formation only in women. Combination of hypertension and overweight increases the risk of all-cause mortality 2.23 times and the risk of cardiovascular mortality 4.0 times, combination of hypertension and hypertriglyceridemia - 2.83 and 5.06 times, combination of overweight and hypertriglyceridemia - 1.73 and 2.99 times, respectively. We detected the additional risk of hypertriglyceridemia in individuals with overweight for all-cause (RR 1.53) and cardiovascular (RR 2.18) mortality risk formation compared with overweight persons with normal level of triglycerides and also the additional risk of hypertriglyceridemia (RR 1.51 and 2.04, respectively) in individuals with hypertension compared with normotensive persons (p&lt;0,05). The additional risk of overweight in individuals with hypertension for all-cause mortality was found only in women (RR 3.23).Conclusion.The independent significant impact of hypertension for all-cause and cardiovascular mortality risk formation was revealed by the results of 27-year prospective study. Combination of hypertension and hypertriglyceridemia increases the risk of all-cause mortality 2.8 times and the risk of cardiovascular mortality 5.1 times, combination of hypertension and overweight - 2.2 and 4 times, combination of overweight and hypertriglyceridemia - 1.7 and 3 times, respectively. We detected the additional risk of hypertriglyceridemia for all-cause mortality in overweight people (RR 1.5) and in individuals with hypertension (RR 1.5). Also, the additional risk of hypertriglyceridemia for cardiovascular mortality risk formation in overweight people (RR 2.2) and in persons with hypertension (RR 2.0) was found.

Characterization of Hepatic Triglyceride Metabolism in the ApcMin/＋ Mouse

The ApcMin/＋ mouse exhibits an intestinal cachexia accompanied by hypertriglyceridemia (HTG). Because the liver governs systemic energy demands through lipid metabolism regulation, the liver is a likely pathological target of HTG in the ApcMin/＋ mouse. Methods: On the basal diet, at 8, 14 and 20 weeks of age, the mice were fasted for 4 h prior to undergoing a hepatic triglyceride production test. Several rate-limiting enzymes and transcription factors participate in hepatic lipid metabolism were determined by RT-qPCR and western blot analysis. Findings: Hepatic de novo lipogenesis (DNL) and β-oxidation were found to be regulated by the AMPK pathway in the ApcMin/＋ mouse at 20 weeks of age. Although hepatic triglyceride production was significantly decreased at 20 weeks of age (p<0.001), hepatic steatosis remained in the ApcMin/＋ mouse. Glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) is governed by the transcription factor octamer-binding transcription factor-1 (Oct-1), which is involved in the nuclear factor-κB (NF-κB) signaling pathway in the liver of the ApcMin/＋ mouse. Additionally, in HepG2 cells, sn50 (an inhibitor of the NF-κB signaling pathway) reversed the tumor necrosis factor α (TNFα)-induced Oct-1 and GPIHBP1 reduction. Interpretation: Our findings indicate that the liver might be responsible for the metabolic complications of HTG in individuals with APC defects and in the ApcMin/＋ mouse. Funding Statement: This work was financially supported by the National Natural Science Foundation of China (Grant No. 31472053 and 31572345) and Graduate Innovation Fund of Jilin University (Grant No. 2017094). The Program for JLU Science and Technology Innovative Research Team (JLUSTIRT, No. 2017TD497 28), the Fundamental Research Funds for the Central Universities. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: All animal welfare and experimental procedures were performed strictly according to the guidelines from the National Institutes of Health Guide for the Care and Use of Laboratory animals (NIH Publications No. 8023, revised 1978). Additionally, the procedures were approved by the Institutional Animal Care and Use Committee of Jilin University under the approved protocol number 201707025.

Non-fat milk attenuates acute hypertriglyceridemia in obese individuals who consume a high fat diet: A randomized control trial

BackgroundRepeated exposure to elevated postprandial triglycerides, as seen with typical Western diets, contributes to atherosclerosis and vascular disease. We determined if a single serving of non-fat milk added to a high fat tolerance test could attenuate postprandial hypertriglyceridemia in individuals who consume a high fat diet. MethodsIn this placebo-controlled, randomized, crossover experimental study, 30 overweight/obese adults consumed a high-fat tolerance test meal combined with either non-fat milk, carbohydrate control drink, or caloric control drink. ResultsPlasma triglycerides increased over time with no significant differences between interventions. Peak plasma triglyceride levels during HFTT were significantly related to dietary fat intake (r = 0.30, p < 0.05). When participants were divided into tertiles based on habitual dietary fat intake, the higher fat diet group exhibited reduced triglyceride net integrated area under the curve when supplemented with non-fat milk. No significant differences in hemodynamic measures (brachial flow-mediated dilation and femoral vascular conductance) were observed between the milk and caloric control trials for either the low fat or high fat diet groups. ConclusionsA single serving of non-fat milk may attenuate acute hypertriglyceridemia in individuals who chronically consume a high fat diet, offering a simple and easily implemented option for managing elevations in postprandial triglycerides.

Postprandial lipid metabolism

Atherogenic effects of postprandial lipoproteins are supported by many studies comparing patients with advanced clinical signs or early markers of cardiovascular disease with subjects without vascular disease. Postprandial lipoprotein abnormalities are more frequent in individuals with type 2 diabetes and other states of insulin resistance, which could be a major factor accounting for the higher rate of cardiovascular diseases observed in these conditions. In patients with type 2 diabetes multiple abnormalities of lipoproteins of both endogenous and exogenous origin are observed also in the presence of good blood glucose control and normal fasting triglyceridaemia, and a direct role of insulin resistance in the development of postprandial dyslipidaemia has been demonstrated. Clinical and experimental studies have demonstrated that a high fat consumption is associated with impaired insulin sensitivity and may worsen postprandial hypertriglyceridemia in individuals with type 2 diabetes and/or hyperlipidaemia. In addition to the amount of fat also the physical structure of the food in which fat is present is able to influence postprandial lipaemia. Data on the effects of dietary fatty acid (FA) modifications in humans are scarce. These studies have provided some evidence that dietary polyunsaturated FA, particularly those of the n-3 class, induce an attenuated postprandial lipaemic response as compared to saturated FA (SFA) and monounsaturated FA (MUFA); however, the data are often conflicting and their interpretation is, generally, controversial. Very little is known in patients with type 2 diabetes, in whom both insulin sensitivity and postprandial lipaemia are particularly relevant. In a medium term (3 weeks) study in type 2 diabetic patients, a MUFA rich diet did not modify insulin sensitivity as compared to the SFA rich diet. The MUFA diet induced a higher early peak of chylomicrons and a significantly lower postprandial response o f small VLDL after a standard test meal, rich in saturated fat. In conclusion, postprandial lipoprotein abnormalities are a frequent feature of type 2 diabetes and of other conditions clustering with insulin resistance. The total amount of fat, more than the specific type of fatty acid, seems to influence postprandial lipoproteins. Data are needed on long term interventions as well as on the interactions between dietary fat and other food components or physical structure. Keywords: postprandial lipoproteins; metabolism of dietary fat