Plasma High-density Lipoprotein Levels Research Articles

Evaluation of the Prevalence and Pattern of Dyslipidemia in Newly Detected Type 2 Diabetes Mellitus Patients and Nondiabetic Controls

Abstract Introduction: Dyslipidemia comprises disorders of lipoprotein metabolism, which is usually characterized by increased plasma levels of total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL), or reduced plasma level of high-density lipoprotein (HDL). Dyslipidemia is commonly found in Type 2 Diabetes Mellitus (T2DM) patients causing an increased risk of atherosclerosis and cardiovascular disease. Many studies done previously show variable prevalence of dyslipidemia (68 to 85 %) in known diagnosed patients of T2DM (with unknown history of onset), however, only limited studies have been done for finding prevalence of dyslipidemia in newly detected T2DM patients. Aim: This study is a cross-sectional observational study done in a tertiary care hospital in Mumbai (India), aiming to study prevalence and pattern in newly detected T2DM patients. The secondary objective is to compare the prevalence and pattern of dyslipidemia in newly detected T2DM patients with non-diabetic controls. Material and Method: For this, 100 newly detected T2DM patients were chosen along with 100 cases of age & gender-matched non-diabetic controls. Their clinical profile and lipid profile of both groups were observed and compared. Result: Results showed higher prevalence of dyslipidemia in newly detected T2DM patients (64%) which was significantly more than the control group (32%). Moreover, the pattern of dyslipidemia showed greater mean levels of TC, TG, and LDL and low mean levels of HDL in T2DM patients compared to the control group. Conclusion: These findings show that there is an increased risk of Dyslipidemia in new onset T2DM patients.

Rosa roxburghii tratt residue as an alternative feed for improving growth, blood metabolites, rumen fermentation, and slaughter performance in Hu sheep.

The utilization of agro-industrial by-products, such as fruit residues, presents a promising strategy for providing alternative feed to ruminants amidst rising prices and limited availability of traditional roughage. In this study, we investigated the effects of Rosa roxburghii tratt residue, a local fruit residue in Guizhou province of China, on the growth, blood metabolites, rumen fermentation, and slaughter performance of Hu sheep. Ninety-six sheep were randomly divided into four groups, namely control, treatment 1, treatment 2, and treatment 3, and fed diets containing 0, 10, 20, and 30% Rosa roxburghii Tratt residue, respectively. Feeding varying levels of Rosa roxburghii Tratt residue showed no significant differences in dry matter intake, average daily gain, or the ratio of dry matter intake to average daily gain. However, sheep in the group fed with 30% Rosa roxburghii Tratt residue showed the highest gross profit. Plasma albumin content was lower in groups fed with Rosa roxburghii Tratt residue-containing diets compared to the control group (p < 0.05). Additionally, diet treatment 3 decreased plasma creatinine levels compared to control and treatment 1 (p < 0.05). Sheep in treatment 2 and treatment 3 exhibited higher plasma high-density lipoprotein level than control and treatment 1 (p < 0.05), as well as increased total cholesterol levels compared to control (p < 0.05). There were no significant differences in other plasma metabolites. Rumen pH, N-NH3, volatile fatty acids, and methane levels did not differ significantly among the four groups. However, feeding diets treatment 2 and treatment 3 resulted in decreased water holding capacity and increased shear force compared to control and treatment 1 (p < 0.05). Furthermore, pH, red chromaticity (a*), yellowness index (b*), and luminance (L*) were unaffected among the four groups of sheep. In conclusion, the inclusion of up to 30% Rosa roxburghii Tratt residue had no adverse effects on growth performance, allowing for feed cost savings without impacting rumen fermentation parameters. Rosa roxburghii tratt residue also showed benefits in improving plasma protein efficiency and enhancing lipid metabolism, albeit with limited effects on meat quality. Considering its affordability, Rosa roxburghii Tratt residue presents a practical choice for low-cost diets, ensuring economic returns.

The ATPase activity of ABCA1 is increased by cholesterol in the presence of anionic lipids.

High-density lipoprotein (HDL) transports excess cholesterol from peripheral tissues back to the liver, and plasma HDL levels are inversely related to cardiovascular disease incidence. ATP-binding cassette A1 (ABCA1) is a member of the ABC protein superfamily, and generates nascent HDL, which consists of several hundreds of phospholipids and cholesterol wrapped by apolipoprotein A-I (apoA-I). However, it remains unclear whether cholesterol is a transport substrate of ABCA1. Since ATP hydrolysis of ABC proteins is typically increased by their transport substrates, we characterized the effects of cholesterol on the ATPase activity of purified ABCA1 using liposomes of various lipid compositions. ABCA1 showed substantial ATPase activity (20-30 nmol∙min-1∙mg-1) only in liposomes containing anionic lipids, including phosphatidylserine. Cholesterol increased the ATPase activity by 1.6- to 3-fold in the presence of anionic lipids. Moreover, phosphatidylserine addition to BHK/ABCA1 cells increased phosphatidylcholine and cholesterol efflux to apoA-I. Next, we investigated the sterol specificity of ABCA1. The ATPase activity of ABCA1 was strongly enhanced by desmosterol and zymosterol, similar to cholesterol. In contrast, 7-dehydrocholesterol and lathosterol weakly increased the ATPase activity, and no increase was observed with stigmasterol or brassicasterol. These findings suggest that ABCA1 transports cholesterol, and prefers cholesterol over plant sterols as a transport substrate.

Dietary supplementation of cinnamaldehyde positively affects the physiology, feed utilization, growth, and body composition of striped catfish Pangasianodon hypophthalmus.

The study evaluated the effects of diverse cinnamaldehyde (CIN) supplementation doses on the physiological attributes, feed utilization, growth, and body composition of striped catfish Pangasianodon hypophthalmus. The study incorporated five doses of CIN supplementation, namely 0, 0.5, 1, 1.5, and 2gkg-1 feed, with four replicates per group. Commercial extruded isonitrogenous and isoenergetic feeds with crude protein and gross energy levels of 28.46% ± 0.23% and 3858.70 ± 18.06kcalkg-1, respectively, were used as test feeds. The initial weight of striped catfish was 5.57 ± 0.02g, and 30 fish were maintained in each cage (2 × 1 × 1 m3) for 60days. The results illustrated that the incorporation of CIN into the diet increases amylase and lipase levels and the ability of striped catfish to accumulate glucose, as the glucose tolerance test revealed that CIN 1.0 and 1.5gkg-1 reduced glucose content to its basal level at 3-4 h postinjection and upregulated the insulin receptor, hexokinase, and hormone-sensitive lipase genes. CIN 1.5gkg-1 also increased plasma total protein and high-density lipoprotein levels and reduced triglyceride and cholesterol levels. CIN 1.0-2.0 g kg-1 increased antioxidant capacity by increasing the levels of superoxide dismutase and glutathione and decreasing malondialdehyde levels. CIN 1.5gkg-1 was the best treatment for increasing final weight, the specific growth rate, protein retention, and the protein efficiency ratio and for decreasing the feed conversion ratio. CIN additionally increased meat protein and decreased meat and liver lipid content. This study concluded that 1.24gkg-1 is the optimal CIN dose calculated from the equation Y = - 0.1487x2 + 0.3702x + 5.0724 (R2 = 0.71) to increase growth and feed efficiency in striped catfish by increasing nonprotein catabolism and exerting antioxidant effects.

Protective effects of swimming exercises and metformin on cardiac and aortic damage caused by a high-fat diet in obese rats with type 2 diabetes, by regulating the Bcl2/Bax signaling pathway.

Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are still being tried. The positive effects of metformin (MET) and physical exercise (EXE) on the pathophysiology of diabetes are well known. In this study, it was aimed to detail these positive effects of MET and EXE in combination on the basis of inflammation, apoptosis mechanisms, and endogen nesfatin-1 (NES-1) synthesis. Twenty-seven type 2 DM (DM-2) male Wistar Albino rats were divided into 4 groups, as the high-fat diet (HFD), MET, EXE, and MET+EXE groups. The total duration of the study was 3 months. At the end of the experiment, blood glucose and lipid profiles were measured. Histopathological evaluation was performed on the cardiac and aortic tissues and apoptotic markers were evaluated immunohistochemically. Inflammatory markers and NES-1 levels were analyzed by enzyme-linked immunosorbent assay. The plasma glucose, homeostatic model evaluation-insulin resistance (HOMA-IR), low-density lipoprotein (LDL) levels increased, and high-density lipoprotein (HDL) levels decreased significantly in the HFD group. In the treatment groups, the glucose, HOMA-IR, LDL, NES-1 levels in the plasma, as well as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, caspase-3 (Cas-3), Bcl-2-associated X protein (Bax), and histopathological findings of inflammation in tissues were decreased. Additionally, there was an increase in plasma insulin, HDL, and tissue B-cell lymphoma-2 and levels. It was observed that the MET and EXE treatments in the DM-2 model reduced cellular damage mechanisms such as inflammation and apoptosis. The decrease in NES-1 levels was thought to be secondary to this antiinflammatory effect. In conclusion, the results demonstrated the effectiveness of EXE in reducing DM-2 and the NES-1 levels. Further studies are needed to evaluate the effect in different EXE models and treatment durations.

High-Density Lipoprotein Inhibits Microvascular and Arterial Thrombosis in Mice By Attenuating VWF Self-Association

Background: Von Willebrand factor (VWF) mediates platelet adhesion and aggregation in primary hemostasis and thrombosis. The thrombogenicity of VWF depends on its self-association into fibers and its ability to efficiently capture platelets under high shear stress. We have shown that high shear promotes self-association of VWF into hyperadhesive strands and fibers, and that this process can be enhanced by low density lipoprotein (LDL) and attenuated by high density lipoprotein (HDL). In a model of thrombotic microangiopathy induced by VWF infusion into ADAMTS13-deficient mice, HDL attenuated the thrombocytopenia induced by the VWF challenge, suggesting that HDL may attenuate other types of thrombosis. Aims: To study the effect of HDL on microvascular and arterial thrombosis in mice by intravital microscopy. Methods: Microvascular thrombosis was induced in ADAMTS13-deficient mice by (1) local stimulation of mesenteric venules with calcium ionophore, and (2) infusion of high doses of recombinant human VWF (rVWF). The effect of HDL on VWF-platelet thrombus formation and deposition in the microvasculature was monitored microscopically. Arterial thrombosis was induced in wild-type (WT) mice by (1) laser-induced cremaster injury, and (2) FeCl 3-induced carotid artery injury. The effect of HDL on arterial thrombosis was also monitored microscopically. Results: When we induced microvascular thrombosis with ionophore, ADAMTS13-deficient mice evinced robust local platelet adhesion, platelet string formation, and thrombus embolization. Time to thrombus resolution was significantly prolonged (about 15 min) compared to that in WT mice (&amp;lt; 5 min). In mice pretreated with HDL (100 mg/kg), platelet deposition was largely prevented, with only occasional single platelets adhering. The differences in the extent of thrombi deposition and time to thrombus resolution between HDL-treated and untreated mice were both statistically significant. In the VWF challenge microvascular thrombosis model, rVWF infusion into ADAMTS13-deficient mice induced platelet adhesion to endothelium-associated VWF fibers in the cremaster microcirculation, forming long strings on the walls of arterioles and venules. Many microvessels became completely occluded. The prothrombotic effect persisted over 90 minutes. In contrast, pretreatment with HDL (100 mg/kg) led to significantly reduced platelet adhesion and string formation. Vessel occlusion was almost completely prevented. When thrombosis was induced in the cremaster arterioles of WT mice, HDL pretreatment resulted in notably decreased platelet accumulation and fibrin deposition in growing thrombi. HDL pretreatment also destabilized the thrombi and led to frequent embolization. In the FeCl 3-induced carotid artery injury model, HDL pretreatment slowed thrombus growth, enhanced thrombus embolization, and delayed vessel occlusion. Conclusion(s): The results demonstrate that VWF self-association is an important mechanism promoting thrombosis in large and small vessels. Our results show that HDL possesses a novel antithrombotic effect by inhibiting VWF self-association, preventing thrombosis in both small and large vessels. These results suggest that increasing the plasma HDL level can be exploited to prevent and treat thrombotic microangiopathies and arterial thrombosis.

S1P content as a characteristic of the cardioprotective properties of HDL in coronary heart disease and diabetes mellitus

Abstract Background Many basic science studies have demonstrated the cardioprotective effect of high-density lipoprotein (HDL). At the same time, several clinical studies in which plasma levels of HDL were pharmacologically increased showed no benefit in cardiovascular risk patients. Accordingly, HDL quantity seems to be less important than HDL quality. Many beneficial effects of HDL are attributed to the bioactive sphingolipid S1P in HDL (HDL-S1P). Purpose In this study, we are now investigating a) the cardioprotective properties of HDL of different patient groups and b) the possibility of loading S1P to restore cardioprotection that may be lacking. Methods HDL was extracted from plasma of diabetic (dmHDL), as well as CHD patients (CHD-HDL) and healthy subjects (healthy HDL) of the same age by ultracentrifugation and injected i.v. into the mouse five minutes before 30 minutes of ischemia (43 mg/KG). This was followed by 24 hours of reperfusion. Systolic cardiac function was determined by ultrasound, infarct size by TTC (2,3,5-triphenyltetrazolium chloride) staining, and S1P levels by mass spectrometry. The level of apolipoprotein M in HDL was determined by ELISA. Results Mice treated with healthy HDL showed smaller infarct size and improved ejection fraction (EF) after I/R than control mice (IS: control 42.95±7.40% [n=26] vs. healthy HDL 33.15±4.68% [n=16], p=0.0001; EF: control 33.68±4.49% vs. healthy HDL 40.00±5.74%, p=0.0016). Treatment with CHD-HDL or dmHDL showed no cardioprotective effects compared to control mice (IS: CHD-HDL 42.22±6.53% [n=16], p=0.9863; dmHDL 43.67±7.81% [n=12], p=0.9899). In both cases, the lack of cardioprotection is associated with lowered HDL-S1P levels (total HDL 210.6±32.6 pmol/mg; CHD-HDL 157.6±49.0 pmol/mg, p=0.0073; dmHDL 171.1±64.7 pmol/mg, p=0.0176). Loading the "sick" HDL with S1P restores cardioprotection only in CHD-HDL (IS: CHD-HDL 42.22±6.53% [n=16] vs. CHD-HDL loaded 32.03±6.45% [n=10], p=0.0023), but not in dmHDL (IS: dmHDL 43.67±7.81% [n=12] vs. dmHDL loaded 38.44±5.98% [n=7], p=0.5110). The very low level of apolipoprotein M (ApoM), responsible for S1P binding, could be a reason for this (total HDL 23.45±6.23 µg/mg [n=15] vs. dmHDL 13.79±4.72 µg/mg [n=14], p=0.0007). Conclusion We highlighted worsened cardioprotection as another characteristic of HDL dysfunction in CHD and in diabetes. This characteristic was based on a lower HDL-S1P content and could be therapeutically corrected by loading S1P in the case of CHD-HDL. A low content of ApoM in dmHDL may prevent successful restoration of cardioprotection by S1P loading.

Abnormal Lipoproteins Trigger Oxidative Stress-Mediated Apoptosis of Renal Cells in LCAT Deficiency.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease caused by the loss of function mutations in the LCAT gene. LCAT deficiency is characterized by an abnormal lipoprotein profile with severe reduction in plasma levels of high-density lipoprotein (HDL) cholesterol and the accumulation of lipoprotein X (LpX). Renal failure is the major cause of morbidity and mortality in FLD patients; the pathogenesis of renal disease is only partly understood, but abnormalities in the lipoprotein profile could play a role in disease onset and progression. Serum and lipoprotein fractions from LCAT deficient carriers and controls were tested for renal toxicity on podocytes and tubular cells, and the underlying mechanisms were investigated at the cellular level. Both LpX and HDL from LCAT-deficient carriers triggered oxidative stress in renal cells, which culminated in cell apoptosis. These effects are partly explained by lipoprotein enrichment in unesterified cholesterol and ceramides, especially in the HDL fraction. Thus, alterations in lipoprotein composition could explain some of the nephrotoxic effects of LCAT deficient lipoproteins on podocytes and tubular cells.

Potential of Hesperidin in the Medicinal Field

Abstract: Hesperidin has gained major interest recently due to the outbreak of COVID-19. The traction has led to more research being conducted on the compound hesperidin. Recent studies have shown its anti-inflammatory and anti-viral attributes, which have beneficial effects on severe acute respiratory syndrome (SARS-CoV-2). Hesperidin has also shown unique effects on the protein of SARS-CoV-2, which lead to a good preventative measure for SARS-CoV-2. Hesperidin also causes a suppression of appetite, which helps to combat obesity through the release of cholecystokinin. Furthermore, hesperidin has shown cardioprotective properties, which cause an increase in plasma high-density lipoprotein levels and a decrease in plasma low-density lipoprotein levels. Hesperidin is also used in combination with the Japanese herb Rikkunshito, which has shown potential in a discovery of a new drug for gastrointestinal motility as hesperidin can depolarize pacemaker potential in interstitial cells of Cajal (ICC). The chemo-preventive effects of hesperidin are caused by its antioxidant effect, which may prevent tissue necrosis due to oxidative stress. The photo-protective effect of hesperidin can reduce the damage to the skin caused by UV rays. Hesperidin also possesses wound-healing properties.

An early screening model of pulse detection technology for hepatic steatosis

BackgroundThe increasing prevalence of hepatic steatosis presents a considerable challenge to public health. There is a critical need for the development of novel preventive and screening strategies for this condition. This study evaluated the potential applications of wrist pulse detection technology for the early detection of liver diseases. The pulse time-domain features of a medical exam population with and without hepatic steatosis were assessed to develop a screening model for this disease. MethodsParticipants were consecutively recruited from March 2021 to March 2022 in the medical examination centers of the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine and the Shanghai Municipal Hospital of Traditional Chinese Medicine. Clinical data from 255 participants, including general information (sex, age, and body mass index), and data related to glucose and blood lipids (fasting plasma glucose, triglyceride, total cholesterol, high-density lipoprotein, and low-density lipoprotein levels) were collected. Wrist pulse signals were acquired using a pulse detection device, and the pulse time-domain features, including t1, t4, t5, T, w1, w2, h2/h1, h3/h1, and h5/h1 were extracted. Participants were assigned to hepatic steatosis and non-hepatic steatosis groups according to their abdominal ultrasound examination results. Their clinical data and pulse time-domain features were compared using chi-square and parametric or non-parametric statistical methods. Three datasets were used to construct screening models for hepatic steatosis based on the random forest algorithm. The datasets for modeling were defined as Dataset 1, containing blood glucose and lipid data and general information; Dataset 2, containing time-domain features and general information; Dataset 3, containing time-domain features, blood glucose and lipid data, and general information. The evaluation metrics, accuracy, precision, recall, F1-score, and areas under the receiver operating characteristic curve (AUC) were compared for each model. ResultsThe time-domain features of the two groups differed significantly. The t1, t4, t5, T, h2/h1, h3/h1, w1, and w2 features were higher in the hepatic steatosis group than in the non-hepatic steatosis group (P < 0.05), while the h5/h1 features were lower in the hepatic steatosis group than in the non-hepatic steatosis group (P < 0.05). The screening models for hepatic steatosis based on both time-domain features and blood glucose and lipid data outperformed those based on time-domain features or blood markers alone. The accuracy, precision, recall, F1-score, and AUC of the combined model were 81.18%, 80.56%, 76.32%, 79%, and 87.79%, respectively. These proportions were 1.57%, 1.86%, 1.76%, 2%, and 3.54% higher, respectively, than those of the model based on time-domain features alone and 3.14%, 4.2%, 2.64%, 4%, and 6.47% higher, respectively, than those of the model based on blood glucose and lipid alone. ConclusionThe early screening model for hepatic steatosis using datasets that included pulse time-domain features achieved better performance. The findings suggest that pulse detection technology could be used to inform the development of a mobile medical device or remote home monitoring system to test for hepatitis steatosis.

Protective Impact of Vanillic Acid on Lipid Profile and Lipid Metabolic Enzymes in Diabetic Hypertensive Rat Model Generated by a High-Fat Diet.

Diabetes is the most common component of metabolic syndrome, including abdominal obesity, insulin resistance, hypertension, and dyslipoproteinemia. This study aims to determine whether vanillic acid has antihyperlipidemic properties in diabetic hypertensive rats. For this study healthy male albino Wister rats (180-220 gm) were selected. A 20-week highfat diet (HFD) was given to produce diabetic hypertension in Wister rats. Control and diabetic hypertensive rats were treated with vanillic acid. Vanillic acid effects on lipid profiles (cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoproteins (HDL)) and lipid metabolizing enzymes LPL, LCAT, and HMG CoA reductase studied by a conventional method. To understand the effect of vanillic acid control, experimental rat lipid and metabolic enzymes were studied and treated and controlled animal liver tissues were observed using the different histology staining agents. Vanillic acid caused considerable lipid profile reductions except for HDL and increased plasma HDL levels. After eight weeks of vanillic acid administration also boosts lipid marker enzyme activity (HMG CoA reductase, LPL, and LCAT). In addition, vanillic acid reduces the accumulation of collagen in liver tissues. These research studies suggest that vanillic acid has antihyperlipidemic effects in diabetic hypertensive rats fed an HFD.

High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner

There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipoprotein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function. Based on neutron reflectometry (NR) and the ability of HDL to efflux cholesterol from macrophages, we confirm these observations and further identify the preference of the S protein for specific lipids and the consequent effects on HDL function on lipid exchange ability. Moreover, the effect of the S protein on HDL function differs depending on the individuals lipid serum profile. Contrasting trends were observed for individuals presenting low triglycerides/high cholesterol serum levels (LTHC) compared to high triglycerides/high cholesterol (HTHC) or low triglycerides/low cholesterol serum levels (LTLC). Collectively, these results suggest that the S protein interacts with the HDL particle and, depending on the lipid profile of the infected individual, it impairs its function during COVID-19 infection, causing an imbalance in lipid metabolism.

HDL - Quo vadis

Many epidemiological studies found low plasma levels of high-density lipoprotein (HDL) cholesterol (HDL-C) associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In cell culture and animal models, HDL particles show many anti-atherogenic actions. However, until now, clinical trials did not find any prevention of ASCVD events by drugs elevating HDL-C levels, at least not beyond statins. Also, genetic studies show no associations of HDL-C levels altering variants with cardiovascular risk. Therefore, the causal role and clinical benefit of HDL-C elevation in ASCVD are questioned. However, the interpretation of previous data has important limitations: First, the inverse relationship of HDL-C with the risk of ASCVD is limited to concentrations < 60 mg/dl (< 1.5 mmol/l). Higher concentrations do not reduce the risk of ASCVD events and are even associated with increased mortality. Therefore, neither the higher-the-better strategies of earlier drug developments nor the assumption of linear cause-and-effect relationships in Mendelian randomization trials are justified. Second, most of the drugs tested so far do not act specifically on HDL metabolism. Therefore, the futile endpoint studies question the clinical benefit of the investigated drugs, but not the importance of HDL in ASCVD. Third, the vascular functions of HDL are not exerted by its cholesterol content (i.e. HDL-C), but by a variety of other molecules. Comprehensive knowledge of the structure-function-disease relationships of HDL particles and their molecules is a prerequisite for testing their physiological and pathogenic relevance and possibly for optimizing the diagnosis and treatment of persons with HDL-associated risk of ASCVD, but also for other diseases, such as diabetes, chronic kidney disease, infections, autoimmune and neurodegenerative diseases.

Adipose Insulin Resistance Associates With Dyslipidemia Independent of Liver Resistance and Involves Early Hormone Signaling.

Adipose tissue insulin resistance is linked to altered plasma levels of triglycerides and HDL (high-density lipoprotein)-cholesterol. However, its degree of independence from liver resistance and different metabolic traits (lipolysis, lipogenesis) effected is not clear and was presently investigated. In 3290 adult subjects, plasma levels of triglycerides and HDL-cholesterol were cross-sectionally measured and related to interindividual variations in measures of insulin resistance in the liver (homeostasis mode assessment of insulin resistance index) or adipose tissue (Adipo-IR index). In subgroups, insulin-induced antilipolysis and lipogenesis in isolated subcutaneous fat cells (n=578) were determined alongside global adipose tissue gene expression (n=132). Using linear regression, homeostasis mode assessment of insulin resistance and Adipo-IR strongly correlated with the plasma lipids explaining 33% of the variations in triglycerides. Together with other variables (age, sex, body mass index, cardiometabolic disorders, nicotine use, ethnicity, and physical activity) in multiple regression, homeostasis mode assessment of insulin resistance, and Adipo-IR each remained an important regressor for triglycerides and HDL-cholesterol (P<0.0001). In fat cells, half-maximum effective concentration but not maximum effect of insulin on antilipolysis and lipogenesis contributed independently to variations in triglycerides and HDL-cholesterol (P=0.001 or lower). This was linked to expression of the insulin receptor, insulin receptor substrate-1, and AKT serine/threonine kinase 2 in adipose tissue. Markers of insulin resistance in the liver and adipose tissue each associate strongly, and independently of each other, to elevated triglycerides and decreased HDL levels. At the fat cell, early insulin receptor signaling and sensitivity, but not maximum insulin action contributes to the variations in circulating triglycerides and HDL-cholesterol.

Identification of Target Genes for Retinoid-related Orphan Receptors Involved in the Suppression of Atherosclerosis

Retinoid-related orphan receptor alpha (RORα) participates in regulating several physiological processes, including metabolism and circadian rhythms. RORα is an important regulator of plasma cholesterol levels and is involved in lipid homeostasis. Its activation increases high-density lipoprotein (HDL) levels and metabolism of oxysterols. RORα-deficient mice develop atherosclerosis owing to decreased plasma HDL levels, increased expression of inflammatory cytokines, and ischemia/reperfusion-induced damage. The transcriptional activity of RORα is controlled by cholesterol and its derivatives, endogenous ligands that form transcription initiation complexes. Conversely, when intracellular cholesterol is reduced by lipid-lowering drugs such as statins, which inhibit cholesterol synthesis, the transcriptional activity of RORα is attenuated. Therefore, studies have focused on identifying target genes regulated by RORα involved in alleviating atherosclerosis to develop new therapies. Characterization of ligands, transcription-mediating factors, and transcription initiation complexes involved in the transcriptional regulation of RORα will facilitate the development of synthetic ligands and their potential applications in diseases such as atherosclerosis, dyslipidemia, and diabetes. In this review, we discuss the current literature on the structure and function of RORα, the target genes regulated by RORα, and the potential of RORα as a therapeutic target for atherosclerosis.

Effect of Eight Weeks of High-Intensity Interval Training Along With Purslane Consumption on Lipid Profile of Rats with Non-alcoholic Fatty Liver Disease

Objective Having physical activity and proper nutrition are very important for preventing Non-Alcoholic Fatty Liver Disease (NAFLD). The present study aims to investigate the effect of eight weeks of high-intensity interval training (HIIT) along with purslane (Portulaca Oleracea) supplementation on the lipid profile of rats with NAFLD Methods In this experimental study, 25 male Wistar rats randomly divided into five groups: healthy control, NAFLD control, supplement, HIIT, and HIIT + supplement. To induce NAFLD, rats received a high-fat diet for 12 weeks. The HIIT was performed for eight weeks, five sessions per week. Plasma levels of High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), Triglyceride (TG) and Total Cholesterol (TC) were measured. One-way ANOVA and Tukey’s post-hoc test were used to analyze the data. Results Plasma level of TG in the HIIT + supplement group were significantly lower than in the NAFLD control group (P=0.035). The TC level in the supplement (P=0.013) and HIIT +supplement (P=0.001) groups was significantly lower than in the NAFLD control group. The HDL level in the HIIT + supplement group was significantly higher compared to healthy control (P=0.021), NAFLD control (P=0.001), HIIT (P=0.006) and supplement (P=0.018) groups. The LDL level in the HIIT (P=0.01), supplement (P=0.001) and HIIT + supplement (P=0.001) groups was significantly lower than in the NAFLD control group. Conclusion It seems that HIIT combined with purslane supplementation can have better effect compared to HIIT and purslane supplementation alone; therefore, this method can be used as a complementary therapy in people with NAFLD.

Improved sperm DNA integrity and altered fat metabolism and intestinal morphology in Nile tilapia (Oreochromis niloticus) males fed rations with purified nucleotide

In this study, we assessed the health, growth, sperm characteristics, and intestinal, liver, and testicular morphology of Nile tilapia (Oreochromis niloticus) males fed rations containing purified nucleotides (NT). A total of 420 females (286 ± 7.15 g) and 140 males (536 ± 13.4 g) were used. Fish were fed on extruded ration (280 g digestible protein kg−1; 11.72 M joule (MJ) of digestible energy kg−1) containing 0.0, 2.5, 5.0, 7.5, and 10.0 g NT kg−1 for 150 days. After mating in hapas, sperm, blood, and tissue samples were collected for spermatic, hematological, biochemical, morphological, and centesimal composition analyses. Males fed on rations containing NT released sperm with a higher (p < 0.05) amount of spermatozoa with undamaged nuclear chromatin and a higher gonadosomatic index (p < 0.05). Growth was not affected (p > 0.05); however, males fed with 7.5 g NT kg−1 presented the smallest (p < 0.05) hepatosomatic index, whereas those fed with any of nucleotide levels had a reduced (p < 0.05) viscerosomatic index. Males fed NT had reduced (p < 0.05) hepatic fat content, and those fed 2.5 and 5.0 g NT kg−1 presented with the lowest (p < 0.05) liver fat content. Visceral fat content was not affected by the ration (p < 0.06). The biochemical composition of the muscle and testis was not affected (p > 0.05) by the ration. Plasma triglyceride levels were reduced (p < 0.05) in males fed the NT diet. Males fed 10 g NT kg−1 had the highest (p < 0.05) plasma high-density lipoprotein (HDL) levels, while those fed 5.0 g NT kg−1 presented the highest (p < 0.05) plasma glucose levels. Hematological parameters were not affected (p > 0.05) by the ration. Males fed 5.0 g NT kg−1 presented the highest (p < 0.05) intestinal viscosity, whereas those fed 2.5 and 5.0 g NT kg−1 had the highest (p < 0.05) enterocytes. The other morphological and morphometric parameters of the intestine, liver, and testis were not affected (p < 0.05) by the ration. The feeding of Nile tilapia breeders with rations of at least 2.5 g NT kg−1 boosted reproductive parameters and provided positive regulation of fish metabolism, resulting in better gonadal and spermatic status as well as a better hepatic and intestinal conditions.

Using adenovirus-mediated gene transfer to study the effect of myeloperoxidase on plasma lipid levels, HDL structure and functionality in mice expressing human apoA-I forms

Apolipoprotein A-I (apoA-I), the main protein component of High-Density Lipoprotein (HDL), is modified in plasma and the arterial wall by various enzymes. Myeloperoxidase (MPO), a leukocyte-derived peroxidase, is highly expressed during inflammation and associates with HDL reducing its functionality and contributing to atherosclerosis. In the present study we sought to explore further the effect of MPO on HDL structure and functionality in vivo using adenovirus-mediated gene transfer of human MPO combined with human apoA-I forms containing substitutions at MPO-sensitive sites or wild type apoA-I. We found that overexpression of MPO in mice significantly increased plasma apoA-I and HDL levels without affecting the expression of genes involved in HDL biogenesis or catabolism in the liver. Overexpression of MPO in the liver reduced the expression of pro-inflammatory genes and increased or did not affect the expression of anti-inflammatory genes suggesting that MPO had no toxic effects in this organ. In the plasma of mice overexpressing MPO, no significant alterations in HDL size or electrophoretic mobility was observed with the exception of mice expressing apoA-I (M148A) which showed enriched pre-β relative to α HDL particles, suggesting that the apoA-I (M148A) mutation may interfere with HDL remodelling. Overexpression of MPO was associated with reduced anti-oxidant capacity of HDL particles in all mice. Interestingly, HDL particles bearing apoA-I (Y192A) showed enhanced ABCA1-dependent cholesterol efflux from macrophages which was not affected by MPO and these mice had reduced levels of LDL-c. These findings provide new insights on the role of specific amino acid residues of apoA-I in HDL structure and function following modification by MPO. This knowledge may facilitate the development of novel therapies based on improved HDL forms for patients with chronic diseases that are characterized by dysfunctional HDL.

Endothelial lipase: regulation and biological function.

Endothelial lipase is synthetized almost exclusively in endothelial cells and then fixed on the luminal surface of the endothelium by means of heparan sulphate proteoglycans. The enzyme is expressed in the endothelium of nearly all tissues and the degree of expression is higher in richly vascularized tissues than in the less vascularized ones. The endothelial lipase expression in tissues is upregulated by shear and cyclic stress, angiotensin II and hypertension. The plasma enzyme level is elevated by pro-inflammatory cytokines, in metabolic syndrome and obesity. Prolonged exercise reduces the plasma enzyme level in the rat. The activity of the enzyme is inhibited by: sphingomyelin, angiopoietin-like protein 3 and 4, and insulin. Endothelial lipase reduces the plasma high density lipoprotein concentration and changes its properties. The enzyme is considered to be the main regulator of the plasma high density lipoprotein concentration. The plasma endothelial lipase concentration is elevated in coronary atherosclerosis and it is inversely correlated with the plasma high density lipoprotein level. The enzyme is considered to exert mostly pro-atherogenic effects. Its action as triglyceride lipase is important in hypertriglyceridemia.

Co-Crystal of Rosiglitazone With Berberine Ameliorates Hyperglycemia and Insulin Resistance Through the PI3K/AKT/TXNIP Pathway In Vivo and In Vitro.

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. This study examined the effect and elucidated the mechanism of improvement of hyperglycemia and insulin resistance by a co-crystal of rosiglitazone with berberine (RB) in high-sugar high-fat diet (HSHFD)-induced diabetic KKAy mice. Methods: Diabetic KKAy mice were randomly divided into seven groups: KKAy model control group (DM control) treated with 3% sodium carboxymethyl cellulose; RB groups, administered daily with RB 0.7 mg/kg (RB-L), 2.11 mg/kg (RB-M), or 6.33 mg/kg (RB-H); positive control groups, administered daily with rosiglitazone 1.04 mg/kg (RSG), berberine 195 mg/kg (BBR), or combination of 1.04 mg/kg RSG and 1.08 mg/kg BBR (MIX). Test compounds were administered orally for 8 weeks. Non-diabetic C57BL/6J mice were used as normal control (NC). Blood glucose, food intake, body weight, glucose-lipid metabolism, and pathological changes in the pancreas and liver were examined. We further evaluated the mechanism of action of RB in C2C12 and HepG2 cells stimulated with high glucose and palmitate. Results: RB treatment improved glucolipid metabolism and insulin resistance in diabetic KKAy mice. RB reduced blood glucose levels, white fat index, plasma triglyceride (TG), low-density lipoprotein (LDL), gastric inhibitory peptide (GIP), and insulin levels, increased the levels of plasma glucagon-like peptide-1 (GLP-1), high-density lipoprotein (HDL), and glycogen content in the liver and muscle; and improved oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and pathological changes in the pancreas and liver of KKAy mice. Moreover, RB upregulated p-PI3K and p-AKT levels and reduced TXNIP expression in KKAy mice and in HepG2 and C2C12 cells. Conclusion: These data indicate that RB ameliorates insulin resistance and metabolic disorders, and the mechanism might be through regulating the PI3K/AKT/TXNIP signaling pathway . Thus, the co-crystal drug RB may be considered as a potential antidiabetic agent for future clinical therapy.