Plasma Low-density Lipoprotein Research Articles

Waist circumference and glycaemia are strong predictors of progression to diabetes in individuals with prediabetes in sub-Saharan Africa: 4-year prospective cohort study in Malawi.

Sub-Saharan Africa is projected to have the highest increase in the number of people with diabetes worldwide. However, the drivers of diabetes in this region have not been clearly elucidated. The aim of this study was to evaluate the incidence of diabetes and the predictors of progression in a population-based cohort with impaired fasting glucose (IFG) in Malawi. We used data from an extensive rural and urban non-communicable disease survey. One hundred seventy-five, of 389 individuals with impaired fasting glucose (IFG) at baseline, age 48 ±15 years and body mass index 27.5 ±5.9 kg/m2 were followed up for a median of 4.2 years (714 person-years). Incidence rates were calculated, and predictors of progression to diabetes were analysed using multivariable logistic regression models, with overall performance determined using receiver operator characteristics (ROC) curves. The median follow-up was 4.2 (IQR 3.4-4.7) years. Forty-five out of 175 (26%) progressed to diabetes. Incidence rates of diabetes were 62.9 per 1000 person-years 95% CI, 47.0-84.3. The predictors of progression were higher; age (odds ratio [OR] 1.48, P = 0.046), BMI (OR 1.98, P = 0.001), waist circumference (OR 2.50,P<0.001), waist-hip ratio (OR 1.40, P = 0.03), systolic blood pressure (OR 1.56, P = 0.01), fasting plasma glucose (OR 1.53, P = 0.01), cholesterol (OR 1.44, P = 0.05) and low-density lipoprotein cholesterol (OR 1.80, P = 0.002). A simple model combining fasting plasma glucose and waist circumference was predictive of progression to diabetes (ROC area under the curve = 0.79). The incidence of diabetes in people with IFG is high in Malawi and predictors of progression are like those seen in other populations. Our data also suggests that a simple chart with probabilities of progression to diabetes based on waist circumference and fasting plasma glucose could be used to identify those at risk of progression in clinical settings in sub-Saharan Africa.

Regulation of low-density lipoprotein on lipid metabolism in macrophages of large yellow croaker (Larimichthys crocea)

Low-density lipoprotein (LDL) is the main carrier of cholesterol transport in plasma, which participates in regulating lipid homeostasis. Studies in mammals have shown that high levels of LDL in plasma absorbed by macrophages trigger the formation of lipid-rich foam cells, leading to the development of atherosclerotic plaques. Although lipid-rich atherosclerosis-like lesions have been discovered in the aorta of several fish species, the physiological function of LDL in fish macrophages remains poorly understood. In the present study, LDL was isolated from the plasma of large yellow croaker (Larimichthys crocea), and mass spectrometry analysis identified two truncated forms of apolipoprotein B100 in the LDL protein profile. Transcriptomic analysis of LDL-stimulated macrophages revealed that differentially expressed genes (DEGs) were enriched in various pathways related to lipid metabolism, as confirmed by the fact that LDL increased total cholesterol and cholesteryl esters content. Meanwhile, the gene and protein expression levels of perilipin2 (PLIN2), a DEG enriched in the PPAR signaling pathway, were upregulated in response to LDL stimulation. Importantly, knocking down plin2 significantly attenuates LDL-induced cholesterol accumulation and promotes cholesterol efflux. Furthermore, the transcription factor PPARγ, which is upregulated in response to LDL stimulation, can enhance the promoter activity of plin2. In conclusion, this study suggests that LDL may upregulate plin2 expression through PPARγ, resulting in cholesterol accumulation in fish macrophages. This study will facilitate the investigation of the function of LDL in regulating lipid homeostasis in macrophages and shed light on the evolutionary origin of LDL metabolism in vertebrates.

Effects of dietary dihydromyricetin on growth performance, antioxidant capacity, immune response and intestinal microbiota of shrimp (Litopenaeus vannamei)

A 56-day culture trial was conducted to evaluate the effects of dietary dihydromyricetin (DMY) on growth performance, antioxidant capacity, immune response and intestinal microbiota of shrimp (Litopenaeus vannamei). 840 healthy shrimp (1.60 ± 0.21 g) in total were fed with four different levels of DMY diets at 0 (Control), 100 (D1), 200 (D2), and 300 (D3) mg/kg, respectively. Samples were collected after the culture trial, and then, a 7-day challenge experiment against Vibrio parahaemolyticus was conducted. The results demonstrated that DMY significantly enhanced the activity of protease, amylase and lipase as well as the expression of lipid and protein transport-related genes (P < 0.05). The results of plasma lipid parameters indicated that DMY reduced lipid deposition, manifested by significantly (P < 0.05) decreased plasma total cholesterol (T-CHO), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). The expression of genes involved in fatty acid β-oxidation and triglyceride catabolism was significantly up-regulated (P < 0.05), and genes involved in triglyceride synthesis were significantly down-regulated in DMY groups when compared to control group (P < 0.05). Moreover, dietary DMY also significantly (P < 0.05) increased the total antioxidant capacity (T-AOC), antioxidant enzymes activity and glutathione (GSH) content of shrimp, and a significant increase of total hemocytes count (THC), phagocytic rate (PR), antibacterial activity (AA) and bacteriolytic activity (BA) was observed in DMY groups (P < 0.05). The addition of DMY to the diet significantly augmented immune response by up-regulating the expression of genes related to toll-like receptors (Toll) signaling pathway, immune deficiency (IMD) signaling pathway and intestinal mucin. Furthermore, dietary DMY could modulate the composition and abundance of intestinal microbiota. In conclusion, DMY showed promising potential as a functional feed additive for shrimp to improve the growth performance and physiological health.

Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathway

ABSTRACT Low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) play a pivotal role by regulating plasma low-density lipoprotein cholesterol (LDL-c) levels. Dihydromyricetin (DMY), the most abundant natural flavonoid in rattan tea, has proven anti-atherogenic effects, but the underlying molecular mechanisms remain poorly understood. Therefore, we studied the effects of DMY on LDLR and PCSK9. The results showed DMY promoted LDLR protein and mRNA expression and increased LDL uptake in HepG2 cells. DMY inhibited intracellular PCSK9 protein and mRNA expression. And it also significantly reduced PCSK9 levels in the cell culture medium. Furthermore, DMY inhibited the expression of PCSK9 through the liver nuclear transcription factor 1 A (HNF1A) and increased the protein expression of LDLR. Taken together, our results support the idea that DMY regulates LDL-c metabolism through PCSK9/LDLR signaling. This study reveals the potential mechanism of DMY’s anti-atherogenic effect and provides a theoretical basis for dietary DMY supplementation.

Alanyl-Glutamine Dipeptide Attenuates Non-Alcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice by Improving Gut Microbiota Dysbiosis.

Non-alcoholic fatty liver disease (NAFLD) manifests as a persistent liver ailment marked by the excessive buildup of lipids within the hepatic organ accompanied by inflammatory responses and oxidative stress. Alanyl-glutamine (AG), a dipeptide comprising alanine and glutamine, is commonly employed as a nutritional supplement in clinical settings. This research aims to evaluate the impact of AG on NAFLD triggered by a high-fat diet (HFD), while concurrently delving into the potential mechanisms underlying its effects. The results presented herein demonstrate a notable reduction in the elevated body weight, liver mass, and liver index induced by a HFD upon AG administration. These alterations coincide with the amelioration of liver injury and the attenuation of hepatic histological advancement. Furthermore, AG treatment manifests a discernible diminution in oil-red-O-stained regions and triglyceride (TG) levels within the liver. Noteworthy alterations encompass lowered plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) concentrations, coupled with elevated high-density lipoprotein cholesterol (HDLC) concentrations. The mitigation of hepatic lipid accumulation resultant from AG administration is aligned with the downregulation of ACC1, SCD1, PPAR-γ, and CD36 expression, in conjunction with the upregulation of FXR and SHP expression. Concomitantly, AG administration leads to a reduction in the accumulation of F4/80-positive macrophages within the liver, likely attributable to the downregulated expression of MCP-1. Furthermore, AG treatment yields a decline in hepatic MDA levels and a concurrent increase in the activities of SOD and GPX. A pivotal observation underscores the effect of AG in rectifying the imbalance of gut microbiota in HFD-fed mice. Consequently, this study sheds light on the protective attributes of AG against HFD-induced NAFLD through the modulation of gut microbiota composition.

Microglia contribute to cognitive decline in hypercholesterolemic LDLr-/- mice.

Familial hypercholesterolemia (FH) is caused by mutations in the gene that encodes the low-density lipoprotein (LDL) receptor, which leads to an excessive increase in plasma LDL cholesterol levels. Previous studies have shown that FH is associated with gliosis, blood-brain barrier dysfunction, and memory impairment, but the mechanisms associated with these events are still not fully understood. Therefore, we aimed to investigate the role of microgliosis in the neurochemical and behavioral changes associated with FH using LDL receptor knockout (LDLr-/-) mice. We noticed that microgliosis was more severe in the hippocampus of middle-aged LDLr-/- mice, which was accompanied by microglial morphological changes and alterations in the immunocontent of synaptic protein markers. At three months of age, the LDLr-/- mice already showed increased microgliosis and decreased immunocontent of claudin-5 in the prefrontal cortex (PFC). Subsequently, 6-month-old male C57BL/6 wild-type and LDLr-/- mice were treated once daily for 30 days with minocycline (a pharmacological inhibitor of microglial cell reactivity) or vehicle (saline). Adult LDLr-/- mice displayed significant hippocampal memory impairment, which was ameliorated by minocycline treatment. Non-treated LDLr-/- mice showed increased microglial density in all hippocampal regions analyzed, a process that was not altered by minocycline treatment. Region-specific microglial morphological analysis revealed different effects of genotype or minocycline treatment on microglial morphology, depending on the hippocampal subregion analyzed. Moreover, 6-month-old LDLr-/- mice exhibited a slight but not significant increase in IBA-1 immunoreactivity in the PFC, which was reduced by minocycline treatment without altering microglial morphology. Minocycline treatment also reduced the presence of microglia within the perivascular area in both the PFC and hippocampus of LDLr-/- mice. However, no significant effects of either genotype or minocycline treatment were observed regarding the phagocytic activity of microglia in the PFC and hippocampus. Our results demonstrate that hippocampal microgliosis, microglial morphological changes, and the presence of these glial cells in the perivascular area, but not increased microglial phagocytic activity, are associated with cognitive deficits in a mouse model of FH.

Reduction of lauric acid content in virgin coconut oil improved plasma lipid profile in high-fat diet-induced hypercholesterolemic mice.

Virgin coconut oil (VCO) is claimed to have various health benefits, but favorable effects of its major component (∼50%), lauric acid, are controversial. Therefore, we aimed to reduce lauric acid content (∼30%) in VCO and evaluate its effect compared to VCO and medium-chain triglycerides (MCT), on food intake, bodyweight (BW), lipid profiles, and hepatic histology. Female C57BL/6 mice were treated with different diets for 3 months: control (normal diet), high-fat diet (HF), HF+VCO, HF+MCT, HF+low lauric acid VCO (LLA), and normal diet+LLA (C+LLA). LLA was prepared by enzymatic interesterification of VCO with methyl octanoate (methyl caprylate) and methyl decanoate (methyl caprate). Plasma and liver lipids, including total cholesterol (TC), high-density lipoprotein (HDL), and triglyceride, were measured by colorimetric assay, and hepatic fat accumulation was examined by oil-red-O staining. HF mice exhibited high plasma and liver TC and low-density lipoprotein (LDL). VCO or MCT treatment lowered liver TC and LDL, whereas LLA increased plasma HDL and markedly improved TC:HDL ratio. The HF-induced hepatic fat accumulation was attenuated by all treatments, of which VCO was the most effective. Control mice administered with LLA demonstrated lower liver TC and LDL, but higher plasma TC and HDL compared to controls. Lowest BW gain and food intake were found in mice treated with LLA. In conclusion, VCO, MCT, and LLA ameliorated hepatic histopathology caused by HF. VCO and MCT improved liver lipid profiles, whereas LLA has more beneficial effect on plasma lipids via a better TC:HDL ratio and showed promise for BW control.

Effect of endo-1,4-beta-xylanase supplementation to low-energy diets on performance, blood constituents, nutrient digestibility, and gene expressions related growth of broiler chickens.

The presence of soluble and insoluble non-starch polysaccharides (NSP) was reported to reduce nutrient utilisation, and adversely impact the broilers' growth performance; accordingly, NSP-degrading enzymes are essential supplements to cereal-based diets. Therefore, the current trial was conducted to characterise the impacts of supplemental xylanase (Xyl) to diets with low-ME levels on performance, carcass traits, blood parameters, nutrient digestibility and some genes expressions in broiler chickens. A total of 600 1-day-old Ross 308 male broiler chicks were randomly assigned to 6 treatments with 10 replications of 10 birds each per group in a completely randomised design. The 6 treatments were as follow: (1) basal diets with balanced ME content served as control (positive control, PC), (2) low-energy diet (negative control 1 [NC1]; ME content reduced by 70 kcal/kg compared with PC), (3) low-energy diet (negative control 2 [NC2]; ME content reduced by 140 kcal/kg compared with PC), (4) NC1 + 100 g/ton xylanase (NC1 + 100Xyl), (5) NC2 + 100 g/ton xylanase (NC2 + 100Xyl), and (6) NC1 + 50 g/ton xylanase (NC1 + 50Xyl). At the end of the experiment (35 days of age), the reduction of energy in the NC diets yielded lower live body weight (BW) and total body weight gain (BWG) (p ˂ 0.001); however, it significantly increased feed intake (p ˂ 0.05), leading to worst feed conversion ratio (FCR) and European production efficiency factor (EPEF) (p ˂ 0.01) than PC. There was non-significant variation in final BW, BWG, FCR, or EPEF between the PC group and the NC groups supplemented with Xyl. Carcass yield, gizzard, liver and, muscle relative weights were not influenced by dietary treatments; while broilers fed diet with low-energy diets with or without Xyl addition had lower abdominal fat (p ˂ 0.01) than PC. Furthermore, broilers fed on low-ME diets supplemented with Xyl showed a reduction in plasma total cholesterol (p ˂ 0.05) and low density lipoprotein (p ˂ 0.01) levels. Greater antibody titre against Newcastle disease (p ˂ 0.05) was recorded in the NC1 + 100Xyl and NC2 + 100Xyl groups. The addition of Xyl to low-energy diets significantly improved (p ˂ 0.05) fibre digestibility compared to the PC group. Moreover, enzyme supplementation increased muscle total lipids content and decreased muscle thiobarbituric acid retroactive substance content. In addition, enzyme supplementation increased gene expression related to growth and gene expression related to fatty acid synthesis. It was concluded that a low-ME diet might diminish broiler performance, whereas Xyl supplementation to low-ME diets beneficially affected growth performance, abdominal fat percentage, nutrient digestibility and immunity for broilers, and gene expressions related to growth and fatty acid synthesis in broiler chickens fed low-energy diets.

Novel soybean polypeptide dglycin alleviates atherosclerosis in apolipoprotein E-deficient mice

Atherosclerosis is a dominant cause of cardiovascular disease. Accumulation of low-density lipoproteins (LDL), formation of foam cells, and endothelial dysfunction within the arterial intima contribute to atherosclerotic plaque formation. Soy consumption is thought to have positive effect on the prevention of atherosclerosis. Therefore, in the present study, a novel soybean polypeptide dglycin was purified and characterized. Oral administration of 20 mg/g.d dglycin reduced 47.6 % lesion area, and 49.1 % lipid deposition in the atherosclerotic plaques in aortic roots in ApoE−/− mice. In addition, it decreased the levels of 26.0 % plasma low-density lipoprotein, 27.2 % triglyceride, 40.1 % cholesterol, 25.1 % malondialdehyde and 24.2 % tumor necrosis factor-alpha (TNFα). In vitro experiments revealed that dglycin inhibited inflammatory cytokine secretion from aortic endothelial cells via the inhibition of NF-κB signaling. Furthermore, it inhibited reactive oxygen species generation, subsequently enhanced cell viability, and protected aortic endothelial cells from necrosis and apoptosis via mitochondrial function improvement. On the other hand, dglycin prevented the uptake of oxidized LDL by macrophages via suppressing the expression of scavenger receptor class A1, which suggested that dglycin prevented foam cell formation. Therefore, dglycin alleviated the early-stage of atherosclerosis via depressing inflammation, lipid deposition, protecting aortic endothelial cells and preventing foam cell formation.

Hypertriglyceridemia-Associated Pancreatitis: New Concepts and Potential Mechanisms.

Triglycerides are a major source of energy, while high plasma triglycerides are a risk factor for various diseases and premature death. Severely elevated plasma triglycerides are a well-established cause of acute pancreatitis with high mortality, likely due to the presence of elevated levels of chylomicrons and large very low-density lipoproteins in plasma. As markedly elevated levels of these very large lipoproteins are not generally found in mild to moderate hypertriglyceridemia, this was previously not regarded as a cause or marker of increased risk of acute pancreatitis. However, mild to moderate hypertriglyceridemia may identify individuals who at a later timepoint develop severe hypertriglyceridemia and acute pancreatitis. We describe measurement of plasma triglycerides and studies on plasma triglycerides and risk of acute pancreatitis. Further, we summarize current European and American guidelines for the prevention of acute pancreatitis and, finally, the potential for future prevention of acute pancreatitis through lowering of plasma triglycerides. Recent observational and genetic studies indicate that mild to moderate hypertriglyceridemia is causally related to increased risk of acute pancreatitis, most likely as a marker of future severe hypertriglyceridemia. Current guidelines do not mention individuals with mild to moderate hypertriglyceridemia, even though newer evidence suggests an unmet medical need. Treatment could include plasma triglyceride-lowering therapy targeting the pathway for lipoprotein lipase as the main triglyceride degrading enzyme in plasma. Angiopoietin-like 3 and apolipoproteinC-III are inhibitors of lipoprotein lipase, and blocking of these 2 inhibitors is showing promising results in relation to marked triglyceride-lowering and could perhaps be used to prevent acute pancreatitis in the future.

Development of Direct LDL Measurement by LDL Precipitation Combined with Sandwich ELISA Using In-House-Generated mAbs.

One of the major risk factors for the progression of cardiovascular diseases is a high blood level of low-density lipoprotein (LDL), so progression of the disease may be prevented by lowering the plasma LDL. Evaluation and monitoring of LDL concentrations are therefore necessary. Friedewald's equation is a calculation method that is currently used routinely to estimate plasma LDL concentrations in hospital laboratories. However, this method cannot be applied to samples with a high concentration of triglyceride (TG). To overcome this limitation, this study aimed to develop direct LDL measurements using in-house generated monoclonal antibodies against human LDL in combination with LDL precipitation using heparin-containing citrate buffer pH 5.04. The method was applied to measure the LDL concentration in 208 randomized samples from Suranaree University of Technology Hospital. The mean values obtained from the developed method and the hospital laboratory were 126.6 ± 43.1 mg/dL and 123.2 ± 42.3 mg/dL, respectively. Linear regression analysis showed a high correlation between these two methods (r = 0.8491, p < 0.0001). High concentrations of TG, total cholesterol, and HDL have no influence on the LDL values obtained by this method. In this study, we offer an alternative technique for the direct measurement of plasma LDL. Further development for more convenient and easy use can now be undertaken.

Effects of Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination on inflammatory responses in atherosclerotic mice

The study aims to observe the effects and explore the mechanisms of Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination in the treatment of the inflammatory response of mice with atherosclerosis(AS) via the Toll-like receptor 4(TLR4)/myeloid differentiation primary response protein 88(MyD88)/nuclear factor-κB(NF-κB) signaling pathway. Male ApoE~(-/-) mice were randomly assigned into a model group, a Buyang Huanwu Decoction group, an Astragali Radix-Angelicae Sinensis Radix combination group, and an atorvastatin group, and male C57BL/6J mice of the same weeks old were used as the control group. Other groups except the control group were given high-fat diets for 12 weeks to establish the AS model, and drugs were administrated by gavage. Aortic intimal hyperplasia thickness, blood lipid level, plasma inflammatory cytokine levels, M1/M2 macrophage markers, and expression levels of proteins in TLR4/MyD88/NF-κB pathway in the vessel wall were measured to evaluate the effects of drugs on AS lesions and inflammatory responses. The results showed that the AS model was successfully established with the ApoE~(-/-) mice fed with high-fat diets. Compared with the control group, the model group showed elevated plasma total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c) levels(P&lt;0.05), thickened intima(P&lt;0.01), and increased plasma tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) levels(P&lt;0.01). Moreover, the model group showed increased expression of vascular cell adhesion molecule-1(VCAM-1) and inducible nitric oxide synthase(iNOS)(P&lt;0.01), inhibited expression of endothelial nitric oxide synthase(eNOS) and cluster of differentiation 206(CD206)(P&lt;0.01), and up-regulated mRNA and protein levels of TLR4, MyD88, NF-κB inhibitor alpha(IκBα), and NF-κB in the vessel wall(P&lt;0.05). Compared with the model group, Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination lowered the plasma TC and LDL-c levels(P&lt;0.01), alleviated the intimal hyperplasia(P&lt;0.01), and reduced the plasma TNF-α and IL-6 levels(P&lt;0.05). Moreover, the two interventions promoted the expression of eNOS and CD206(P&lt;0.05), inhibited the expression of VCAM-1 and iNOS(P&lt;0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, IκBα, and NF-κB(P&lt;0.05) in the vessel wall. This study indicated that Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination could delay the progression of AS, inhibit the polarization of vascular wall macrophages toward M1 type, and attenuate vascular inflammatory response by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway in the vascular wall. Astragali Radix and Angelicae Sinensis Radix were the main pharmacological substances in Buyang Huanwu Decoction for alleviating the AS vascular inflammatory response.

Sialidase-induced desialylation of blood plasma low-density lipoproteins in mice

Sialidase-induced desialylation of blood plasma low-density lipoproteins in mice

High-fat diet causes hepatic steatosis, increased plasma low-density lipoprotein levels, and alters the PCSK9-lDLR system more pronouncedly than a high-carbohydrates diet in rats

High-fat diet causes hepatic steatosis, increased plasma low-density lipoprotein levels, and alters the PCSK9-lDLR system more pronouncedly than a high-carbohydrates diet in rats

Low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand factor self-association

Abstractvon Willebrand factor (VWF) mediates primary hemostasis and thrombosis in response to hydrodynamic forces. We previously showed that high shear promoted self-association of VWF into hyperadhesive strands, which can be attenuated by high-density lipoprotein (HDL) and apolipoprotein A-I. In this study, we show that low-density lipoprotein (LDL) binds VWF under shear and enhances self-association. Vortexing VWF in tubes resulted in its loss from the solution and deposition onto tube surfaces, which was prevented by HDL. At a stabilizing HDL concentration of 1.2 mg/mL, increasing concentrations of LDL progressively increased VWF loss, the effect correlating with the LDL-to-HDL ratio and not the absolute concentration of the lipoproteins. Similarly, HDL diminished deposition of VWF in a post-in-channel microfluidic device, whereas LDL increased both the rate and extent of strand deposition, with both purified VWF and plasma. Hypercholesterolemic human plasma also displayed accelerated VWF accumulation in the microfluidic device. The initial rate of accumulation correlated linearly with the LDL-to-HDL ratio. In Adamts13−/− and Adamts13−/−LDLR−/− mice, high LDL levels enhanced VWF and platelet adhesion to the myocardial microvasculature, reducing cardiac perfusion, impairing systolic function, and producing early signs of cardiomyopathy. In wild-type mice, high plasma LDL concentrations also increased the size and persistence of VWF-platelet thrombi in ionophore-treated mesenteric microvessels, exceeding the accumulation seen in similarly treated ADAMTS13-deficient mice that did not receive LDL infusion. We propose that targeting the interaction of VWF with itself and with LDL may improve the course of thrombotic microangiopathies, atherosclerosis, and other disorders with defective microvascular circulation.

The Triglycerides-Glucose Index Shows a Stronger Correlation with Serum Adiponectin Levels than Homeostasis Model Assessment of Insulin Resistance and Quantitative Insulin Sensitivity Check Index.

Purpose: To evaluate the association between diverse surrogate markers of insulin resistance and adiponectin concentrations. Methods: Four hundred healthy participants were included. Two different cohorts were formed according to the body mass index (BMI) values. Group 1 (n = 200) consisted of individuals with normal BMI values (18.50-24.99 kg/m2), whereas in Group 2 (n = 200) there were overweight or obese individuals (BMI ≥25.00 kg/m2). Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and triglycerides-glucose index (TyG) were calculated. Serum adiponectin levels were measured by ELISA. A correlation analysis was performed to assess the association between serum adiponectin and HOMA-IR, QUICKI, and TyG. Results: Participants in Group 2 were older (age in years: Group 1, 33.3 ± 6.8 vs. Group 2, 36.4 ± 7.0, P < 0.001). There was no gender difference between groups. Overweight or obese participants had higher BMI, waist circumference, fat mass, fat ratio, fasting plasma glucose, fasting plasma insulin, triglycerides, total cholesterol, and low-density lipoprotein cholesterol values, whereas high-density lipoprotein cholesterol was higher in participants with normal BMI measures. Overweight or obese subjects were more insulin resistant (higher TyG index and HOMA-IR) and less insulin sensitive (lower QUICKI), P < 0.001 for all. Serum adiponectin levels were lower in Group 2 (serum adiponectin in ng/mL: Group 1, 11,880 ± 6838 vs. Group 2, 9115 ± 5766, P < 0.001). The correlation between TyG index and adiponectin was stronger than the correlation between QUICKI and adiponectin, and HOMA-IR and adiponectin (r for TyG and adiponectin -0.408, r for QUICKI and adiponectin 0.394, r for HOMA-IR and adiponectin -0.268, respectively, P < 0.001 for all correlations). Conclusions: TyG has a stronger association with adiponectin than HOMA-IR and QUICKI.

Regulation of cholesterol metabolism during high fatty acid–induced lipid deposition in calf hepatocytes

Cholesterol in the circulation is partly driven by changes in feed intake, but aspects of cholesterol metabolism during development of fatty liver are not well known. The objective of this study was to investigate mechanisms of cholesterol metabolism in calf hepatocytes challenged with high concentrations of fatty acids (FA). To address mechanistic insights regarding cholesterol metabolism, liver samples were collected from healthy control dairy cows (n = 6; 7-13 d in milk) and cows with fatty liver (n = 6; 7-11 d in milk). In vitro, hepatocytes isolated from 3 healthy female calves (1 d old) were challenged with or without a mix of 1.2 mM FA to induce metabolic stress. In addition, hepatocytes were processed with 10 µmol/L of the cholesterol synthesis inhibitor simvastatin or 6 µmol/L of the cholesterol intracellular transport inhibitor U18666A with or without the 1.2 mM FA mix. To evaluate the role of cholesterol addition, hepatocytes were treated with 0.147 mg/mL methyl-β-cyclodextrin (MβCD + FA) or 0.147 mg/mL MβCD with or without 10 and 100 µmol/L cholesterol before incubation with FA (CHO10 + FA and CHO100 + FA). In vivo data from liver biopsies were analyzed by 2-tailed unpaired Student's t-test. Data from in vitro calf hepatocytes were analyzed by one-way ANOVA. Compared with healthy cows, blood plasma total cholesterol and plasma low-density lipoprotein cholesterol content in cows with fatty liver was markedly lower, whereas the hepatic total cholesterol content did not differ. In contrast, compared with healthy controls, the triacylglycerol content in the liver and the content of FA, β-hydroxybutyrate, and aspartate aminotransferase in the plasma of cows with fatty liver were greater. The results revealed that both fatty liver in vivo and challenge of calf hepatocytes with 1.2 mM FA in vitro led to greater mRNA and protein abundance of sterol regulatory element binding transcription factor 1 (SREBF1) and fatty acid synthase (FASN). In contrast, mRNA and protein abundance of sterol regulatory element binding transcription factor 2 (SREBF2), acyl coenzyme A-cholesterol acyltransferase, and ATP-binding cassette subfamily A member 1 (ABCA1) were lower. Compared with the FA group, the cholesterol synthesis inhibitor simvastatin led to greater protein abundance of microsomal triglyceride transfer protein and mRNA abundance of SREBF2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), ACAT2, and lower ABCA1 and FASN protein abundance. In contrast, compared with the FA group, the cholesterol intracellular transport inhibitor U18666A + FA led to greater total cholesterol concentration and greater protein and mRNA abundance of FASN. Compared with the MβCD + FA group, the addition of 10 µmol/L cholesterol led to greater concentration of cholesteryl ester and excretion of apolipoprotein B100, and greater protein and mRNA abundance of ABCA1 and microsomal triglyceride transfer protein, and lower concentration of malondialdehyde. Overall, a reduction in cholesterol synthesis promoted FA metabolism in hepatocytes likely to relieve the oxidative stress caused by the high FA load. The data suggest that maintenance of normal cholesterol synthesis promotes very low-density lipoprotein excretion and can reduce lipid accumulation and oxidative stress in dairy cows that experience fatty liver.

Chrysin 7-O-β-d-glucopyranoside increases hepatic low-density lipoprotein receptor expression through AMP-activated protein kinase activation.

Elevated plasma low-density lipoprotein (LDL) cholesterol level is a risk factor for developing atherosclerosis. Increased LDL receptor (LDLR) expression is expected to reduce the risk of atherosclerotic disease since hepatic LDLR is essential for clearing plasma LDL cholesterol. Here, we screened human LDLR promoter effectors and observed that extracts from peduncles of sweet cherry (Prunus avium) 'Sato-Nishiki' induce LDLR gene promoter activity. We used several analytical and chemical methods to show that chrysin 7-O-β-d-glucopyranoside (chrysin-7G) is one of the compounds that stimulate LDLR gene promoter activity in cherry peduncle extracts. Furthermore, synthetic chrysin-7G increased the expression and activity of LDLR. The chrysin-7G-mediated increase in LDLR expression and activity was completely abolished by treatment with an AMP-activated protein kinase (AMPK) inhibitor, compound C. These results indicate that chrysin-7G increases LDLR expression through AMPK activation and may be a useful compound that can be recycled from waste parts of agricultural products.

Investigation the impact of liraglutide on the thyroid function tests

Aim: Liraglutide is a once-daily glucagon-like peptide-1 receptor agonist (GLP‑1 RA) which is an incretin hormone secreted from intestinal L cells in response to nutritional intake and stimulates glucose-dependent insulin secretion, decreases hepatic glucagon secretion, slows gastric emptying, provides a feeling of satiety and is the first GLP‑1 RA to be indicated for weight loss treatment for obesity. The impact of liraglutide on thyroid function tests is unknown and to the best of our knowledge, there are no studies on this regard. Our aim is to compare thyroid function tests, other biochemical and hemogram parameters before and 6 months after liraglutide treatment.&#x0D; Material and Methods: The patients, 18-65 years old, who used liraglutide for at least 6 months due to obesity treatment between January 2021 and January 2023 in Burdur State Hospital were included.&#x0D; Results: There were 51 patients (39 female, 12 male) using liraglutide without thyroid disease during the study period. Twelve patients discontinued liraglutide use before the 6th month of treatment was completed. Weight, body mass index (BMI), fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), low-density lipoprotein (LDL), triglyceride and thyroid-stimulating hormone (TSH) values were significantly lower at the 6th month of treatment. Free thyroxine (FT4) and free triiodothyronine (FT3) values were similar. and there was no difference other biochemical and hemogram parameters between before and 6 months after treatment&#x0D; Conclusion: We found a significant decrease in TSH values and improvement in metabolic parameters, but no change in thyroid hormone levels.

Advanced progress of the relationship between PCSK9 monoclonal antibodies and hyperglycemic adverse events.

Long-term use of statins had been confirmed to cause an increase in hyperglycemic adverse events (HAEs), whose mechanism has been well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (PCSK9-mAbs), a kind of new lipid-lowering drug, can effectively reduce plasma low-density lipoprotein cholesterol levels in patients with CHD and have been widely used. However, animal experiments, Mendelian randomization studies, clinical researches and Meta-analyses which focused on the relationship between PCSK9-mAbs and HAEs had reached different conclusions, which has attracted great attention from clinicians. The newest FOURIER-OLE randomized controlled trial followed PCSK9-mAbs users for over 8 years, whose results suggested that long-term use of PCSK9-mAbs did not increase the incidence of HAEs. Newest Meta-analyses also indicated that there was no relationship between PCSK9-mAbs and NOD. Meanwhile, genetic polymorphisms and variants related to PCSK9 might have effects on HAEs. According to the results of current studies, there is no significant relationship between PCSK9-mAbs and HAEs. However, longer-term follow-up studies are still needed to confirm it. Although PCSK9 genetic polymorphisms and variants may affect the possible occurrence of HAEs, there is no need to perform relevant genetic testing before applying PCSK9-mAbs.