Search Results (184)

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

Background: Childhood obesity is a significant global health concern. Butyrylcholinesterase (BChE) has been shown to play a role in lipid metabolism. This study aimed to assess BChE activity, obesity-related and lipid-related indices, and dyslipidemia in obese and non-obese children, and to investigate the associations of these parameters with obesity among Thai children. Methods: The study included 661 Thai children, consisting of 338 with obesity and 323 with a normal weight. Anthropometric measurements, metabolic parameters, obesity- and lipid-related indices, and BChE activity were evaluated. Results: The obese group exhibited significantly higher BChE activity and obesity-related and lipid-related indices compared to the non-obese group (p < 0.01). Additionally, metabolic parameters—including glucose levels, triglyceride-glucose (TyG) index, and TyG-related indices—as well as the lipid profile, which included triglycerides (TG), non-high-density lipoprotein cholesterol (non-HDL-C), and very-low-density lipoprotein cholesterol (VLDL-C), were all significantly elevated in the obese group (p < 0.01). Obesity was associated with dyslipidemia (p < 0.01). Moreover, BChE activity showed a positive correlation with obesity-related and lipid-related indices, along with several metabolic parameters (p < 0.002). The upper stratum of BChE activity (OR = 5.356), the non-HDL-C/HDL-C ratio (OR = 2.185), and the TG/HDL-C ratio (OR = 1.703) were found to be effective in evaluating and predicting the risk of obesity, even after adjusting for potential covariates (p < 0.01). Conclusions: These findings indicate a significant relationship between obesity and increased BChE activity, lipid-related indices, and dyslipidemia in Thai children. Therefore, changes in BChE activity may be considered a factor associated with obesity, enhancing its potential as a marker for obesity assessment. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive accumulation of triglycerides and other lipids within liver cells and is closely associated with cardiovascular disease and metabolic syndrome. Very low-density lipoprotein (VLDL) is a lipoprotein synthesized and secreted by the liver and is primarily responsible for transporting triglycerides from the liver to peripheral tissues. Therefore, there is a strong association between MASLD and VLDL. Studies have found that excess production and abnormal metabolism of VLDL can lead to elevated blood triglyceride levels, which in turn promote fat deposition in the liver, leading to MASLD. During the pathophysiological process of MASLD, adipokines and inflammatory mediators secreted by adipose tissue can affect the metabolic network of the liver, further aggravating VLDL metabolic disorders. This paper reviews the effects of VLDL synthesis and metabolism on the development of MASLD, including the changes in VLDL structure and composition, the biosynthesis of VLDL, and the mechanism of underlying VLDL-associated damage, in an attempt to elucidate the intricate crosstalk between MASLD and VLDL, in order to provide new perspectives and methods for the prevention and treatment of related diseases. Full article

Dyslipidemia is a well-known risk factor in the development and progression of atherosclerosis. VLDL plays a crucial role in maintaining lipid homeostasis; however, even minor fluctuations in its production, intracellular trafficking, and secretion can contribute to the progression of atherosclerosis. Fenofibrate is an FDA-approved drug that effectively lowers plasma triglycerides and VLDL-associated cholesterol while simultaneously increasing HDL levels. Although fenofibrate is a known PPARα agonist with several proposed mechanisms for its lipid-altering effects, its impact on the intracellular trafficking of VLDL has not yet been investigated. We observed that treatment of HepG2 cells with 50 µM of fenofibrate resulted in a significant reduction in VLDL secretion, as evidenced by a significant decrease in the secretion of ³H-labeled TAG, fluorescent TAG, and ApoB100 protein into the media. Using confocal microscopy to monitor VLDL intracellular trafficking, we observed a distinct change in VLDL triglyceride localization, suggesting delayed transport through the endoplasmic reticulum and Golgi. An immunoblot analysis revealed a decrease in Sar1B protein expression, a key regulator of COPII protein recruitment, which is essential for VTV formation and intracellular VLDL trafficking, the rate-limiting step in VLDL secretion. Our data reveal a novel mechanism by which fenofibrate alters the lipid profile by interfering with intracellular VLDL trafficking in hepatocytes. Full article

Background/Objectives: Vitamin D deficiency in children has been linked to various metabolic disturbances, including dyslipidemia, which contributes to cardiovascular risk. This study aims to investigate the relationship between vitamin D levels and lipid profiles in children. Methods: A cohort of 332 children with either normal vitamin D or diagnosed vitamin D deficiency was recruited. Serum vitamin D levels were measured, and lipid profiles, including total cholesterol, low-density lipoproteins (LDLs), high-density lipoproteins (HDLs), and triacylglycerols (TAGs), were assessed. The data were analyzed using statistical methods. Results: This study found that children with higher serum vitamin D concentrations had significantly lower TAG (p = 0.033) and very-low-density lipoprotein (VLDL) (p = 0.038) levels and higher HDL levels (p = 0.042), indicating a more favorable lipid profile compared to those with lower vitamin D levels. Conclusions: This study demonstrates that vitamin D deficiency can be associated with dyslipidemia in children. These findings suggest that vitamin D supplementation may be an effective strategy for managing dyslipidemia and reducing cardiovascular risk in pediatric populations. Further research is needed to determine the long-term effects and optimal dosing of vitamin D in this context. Full article

Background: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the accumulation of fat in the liver without excessive alcohol consumption or other known liver diseases. MASLD is the most common liver disease in adolescents with obesity. The aims of this study were as follows: (i) to determine which index (waist circumference BMI, WHtR, VAI, METS-IR, METS-VF, HSI, FLI, or MetS_zscore) best explains the prevalence of MASLD in adolescents with obesity; (ii) to determine whether there was a specific index that was most strongly associated with MASLD; (iii) to assess which liver function indexes were most strongly correlated with MASLD. Methods: A total of 758 adolescents with severe obesity (BMI z-score > 2) admitted at the Division of Auxology, Istituto Auxologico Italiano, IRCCS, Piancavallo-Verbania for a 3-week multidisciplinary body weight reduction program were selected. Anthropometric parameters (stature, body mass, BMI, and waist and hip circumference) were collected, and body composition (lean and fat mass) was determined using the tetrapolar bioimpedance analysis (BIA) technique. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides (TG), and C-reactive protein (CRP) were measured using standard techniques. MASLD was diagnosed based on abdominal ultrasound results. Results: WHtR (65.76%) was the most sensitive compared with other indexes. The HSI (AUC: 0.67 (0.63–0.71, 95% CI), p-value < 0.05) showed the best performance in predicting MASLD, with the threshold for having MASLD considered at 48.22. The indexes that showed the worst performance in predicting MASLD were the MetS z-score (AUC: 0.56 (0.52–0.60)) and the VAI (AUC: 0.57 (0.52–0.61)). ALT (OR: 2.92 (2.29–3.77); 95% CI) and AST (OR: 2.52 (2.03–3.20)) were the parameters with a stronger correlation with MASLD. Conclusions: The most sensitive index for diagnosing MASLD was the WHtR, based exclusively on anthropometric parameters. HSI was the index that correlated the most with MASLD, while the parameters of liver function (ALT and AST) were the most strongly correlated with the disease and its severity. Full article

Diabetes mellitus is a chronic, degenerative, and multifactorial disease characterized by hyperglycemia, and at least 537 million people suffered from diabetes in 2021. Agave durangensis Gentry, a species of agave native to the state of Durango, reports phenolic compounds, flavonols, flavonoids, and saponins and could be an alternative for the treatment of diabetes. The aim of this work was to identify the compounds in the leaves of Agave durangensis Gentry and their potential activity in diabetes. The leaf extract of Agave durangensis Gentry (EAD) was characterized by ultra-performance liquid chromatography–mass spectrometry (UPLC-MS), and different families of bioactive compounds were quantified by analytical methods. Probable pharmacological targets were identified in silico, and the inhibition of dipeptidyl peptidase-4 (DPP4) was validated in vitro. A model of hyperglycemia was established with streptozotocin in male Wistar rats, and we administered EAD intragastrically at a dose of 300 mg/kg, as well as combinations of the extract with metformin and sitagliptin over 30 days. Biochemical and histological parameters were analyzed. We identified thirty-six major compounds, where triterpenes represented 30% of the extract. Molecular docking showed that the extract could interact with α-glucosidases and DPP4 since a large number of compounds in the extract have a Δ G lower than that reported for the controls, and DPP4 inhibition was confirmed by in vitro assays. In vivo assays demonstrated that the administration of the extract was able to significantly decrease glucose levels by 56.75% and glycosylated hemoglobin by 52.28%, which is higher than that reported for sitagliptin with a decrease of 35.22%. In addition, the extract decreased triglycerides by 59.28% and very-low-density lipoprotein (VLDL) cholesterol by 60.27%, and when administered in combination with metformin, it decreased them more than when metformin was administered alone. For all the above reasons, Agave durangensis Gentry extract could be used for the development of phytomedicine for the treatment of diabetes. Full article

The liver plays a crucial role in maintaining lipid homeostasis by converting toxic free fatty acids into VLDL, which the body uses for energy. Even minor changes in VLDL formation and secretion can result in serious health conditions such as atherosclerosis and non-alcoholic fatty liver disease. Despite the importance of VLDL, the proteins and signaling pathways involved in its regulation remain largely unknown. This study aims to develop a novel methodology to study intracellular VLDL transport events and explore the role of liver fatty acid-binding protein (LFABP) in VLDL transport and secretion. Current methods to study VLDL are often tedious, time-consuming, and expensive, underscoring the need for an alternative approach. We designed a new immunofluorescence-based assay to track the formation and secretion of VLDL in cells over time using fluorescently tagged TopFluor oleic acid. Confocal microscopy confirmed that TopFluor oleic acid enters hepatocytes and colocalizes with the ER, Golgi, and plasma membrane. Additionally, the collection of cell culture media revealed that TopFluor was incorporated into VLDL particles, as confirmed by fluorescence readings and ApoB100 immunoblots. This novel assay provides a valuable tool for further research into the mechanisms of VLDL regulation and the development of potential therapeutic targets for related diseases. Utilizing this assay, we identified LFABP as a key regulatory protein in post-Golgi VLDL trafficking. Our data suggest that LFABP plays a crucial role in this process, and its functional impairment leads to reduced VLDL secretion. Full article

There is growing evidence linking growth differentiation factor 15 (GDF15) to both metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular (CV) risk. Nevertheless, the potential relationship between circulating levels of GDF15 and key features of MASLD being predisposed to atherosclerotic CV disease is not fully unveiled. The aim of this study was to deepen into the role of circulating GDF15 levels on metabolic-associated liver injury and atherosclerotic CV disease. We determined the serum GDF15 levels in 156 participants of a metabolic patient-based cohort, and cross-sectionally explored its associations with liver injury and an advanced atherosclerotic lipoprotein profile assessed by nuclear magnetic resonance (¹H-NMR). Additionally, we prospectively evaluated the association between GDF15 levels at baseline and incident atherosclerotic CV disease after a 10-year follow-up. GDF15 was related to liver injury and inflammatory hallmarks, and it increased the likelihood for liver steatosis independently of confounding factors. Likewise, GDF15 was positively associated with an atherogenic profile, particularly with the number of very-low-density lipoproteins (VLDL) particles and its cholesterol and triglyceride content, and with an indicator of subclinical atherosclerosis (i.e., carotid intima–media thickness (cIMT)). The baseline serum GDF15 levels were higher in the patients with atherosclerotic CV disease (10.6%) after a 10-year follow-up than in the individuals without CV disease. Altogether, this study provides new insights into the role of GDF15 in both MASLD and CV disease. Full article

Background: Cytochrome P450 2B6 (CYP2B6) is a sexually dimorphic, anti-obesity CYP enzyme responsible for the metabolism of xeno- and endobiotics, including the metabolism of polyunsaturated fatty acids (PUFAs) into 9-hydroxyoctadecadienoic acid (9-HODE) and 9-hydroxyoctadecatrienoic acid (9-HOTrE). However, humanized CYP2B6 transgenic (hCYP2B6-Tg) mice are sensitive to diet-induced hepatic steatosis despite their resistance to obesity. The purpose of this study was to determine if 9-HODE, 9-HOTrE, or other factors contribute to the sexually dimorphic steatosis observed in hCYP2B6-Tg mice. Results: Cyp2b9/10/13-null (Cyp2b-null) mice were injected with either 9-HODE or 9-HOTrE for 2 days and were then subjected to a fasting period of 20 h to induce steatosis. Serum lipids were moderately increased, especially in females, after 9-HODE (triglycerides (TGs), very low-density lipoproteins (VLDLs)) and 9-HOTrE (high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), cholesterol) treatment. No change in hepatic lipids and few changes in hepatic gene expression were observed in mice treated with either oxylipin, suggesting that these oxylipins had minimal to moderate effects. Therefore, to further investigate CYP2B6’s role in steatosis, hCYP2B6-Tg and Cyp2b-null mice were subjected to a 20 h fast and compared. Both male and female hCYP2B6-Tg mice exhibited increased steatosis compared to Cyp2b-null mice. Serum cholesterol, triglycerides, HDLs, and VLDLs were increased in hCYP2B6-Tg males. Serum triglycerides and VLDLs were decreased in hCYP2B6-Tg females, suggesting the greater hepatic retention of lipids in females. Hepatic oxylipin profiles revealed eight perturbed oxylipins in female hCYP2B6-Tg mice and only one in males when compared to Cyp2b-null mice. RNA-seq also demonstrated greater effects in females in terms of the number of genes and gene ontology (GO) terms perturbed. There were only a few overlapping GO terms between sexes, and lipid metabolic processes were enriched in hCYP2B6-Tg male mice but were repressed in hCYP2B6-Tg females compared to Cyp2b-nulls. Conclusions: hCYP2B6-Tg mice are sensitive to fasting-mediated steatosis in males and females, although the responses are different. In addition, the oxylipins 9-HODE and 9-HOTrE are unlikely to be the primary cause of CYP2B6’s pro-steatotic effects. Full article

Background: Recently, we reported that longer-term mixed nut intake significantly reduced serum total and low-density lipoprotein (LDL)-cholesterol, but these markers may not fully capture lipoprotein-related cardiovascular disease (CVD) risk. Objectives: This randomized, controlled, single-blinded, crossover trial in older adults with overweight or obesity examined the effects of longer-term mixed nut consumption on lipoprotein particle size, number, and lipid distribution. Methods: Twenty-eight participants (aged 65 ± 3 years; BMI 27.9 ± 2.3 kg/m²) completed two 16-week periods (control [no nuts] vs. mixed nuts (60 g/day: 15 g of walnuts, pistachios, cashews, and hazelnuts), separated by an 8-week washout. Plasma lipoprotein particle numbers, sizes, and lipid distributions across subclasses were analyzed using high-throughput nuclear magnetic resonance (NMR) spectroscopy. Results: Mixed nut consumption significantly reduced Apolipoprotein B (ApoB) concentrations (−0.07 g/L; p = 0.009), total cholesterol (−0.27 mmol/L; p = 0.047), non-HDL cholesterol (−0.28 mmol/L; p = 0.022), and total triacylglycerol (TAG) (−0.27 mmol/L; p = 0.008). Total very large-density lipoprotein (VLDL) particle numbers decreased by 24 nmol/L (p < 0.001), with reductions observed across all VLDL subclasses. Total LDL particle numbers (p = 0.044), specifically intermediate-density lipoprotein (IDL) (p = 0.002) and large LDL particles (p = 0.015), were also reduced, while HDL particle numbers and sizes were unaffected. The mixed nut intervention significantly reduced cholesterol concentrations across all VLDL subclasses and IDL (all p < 0.01), with no changes in LDL or HDL subclasses. TAG concentrations showed reductions across all lipoprotein subclasses (all p < 0.05). Conclusions: Longer-term mixed nut consumption may lower CVD risk in older adults and favorable shifts in apoB-containing lipoprotein subclasses towards a less atherogenic profile. Full article

Background: Brassica nigra possesses a significant concentration of bioactive compounds and has been demonstrated to have a variety of pharmacological properties, although its sprout has not been extensively studied. Thus, the protective effects of Brassica nigra sprout hydroalcoholic extract (BNSE) on lipid homeostasis, hepatotoxicity, and nephrotoxicity in cyclophosphamide (CYP)-induced toxicity in rats were examined in this study. Methods: Four experimental rat groups (n = 8 for each group) were examined as follows: NR, normal rats that received normal saline by oral gavage daily; CYP, injected with a single dose of CYP at 250 mg kg⁻¹ intraperitoneally (i.p.) and did not receive any treatment, receiving only normal saline by oral gavage daily; CYP + BNSE250, injected with a single dose of CYP at 250 mg kg⁻¹ i.p. and treated with BNSE at 250 mg kg⁻¹ by oral gavage daily for three weeks; and CYP + BNSE500, injected with a single dose of CYP at 250 mg kg⁻¹ i.p. and treated with BNSE at 500 mg kg⁻¹ by oral gavage daily for three weeks. Results: The results indicated a significant increase (p < 0.05) in triglyceride (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), and very low-density lipoprotein cholesterol (VLDL-c) levels in CYP-induced toxicity rats. The administration of BNSE at 250 and 500 mg kg⁻¹ significantly (p < 0.05) attenuated TG, CHO, LDL-c, and VLDL-c at values comparable with the NR group. The most efficient treatment for improving the lipid profile and atherogenicity complication was BNSE at 500 mg kg⁻¹, performing even better than 250 mg kg⁻¹. Administrating BNSE at 250 or 500 mg kg⁻¹ improved the liver’s function in a dose-dependent manner. Comparing the lower dose of 250 mg kg⁻¹ of BNSE with 500 mg kg⁻¹ showed that administrating 250 mg kg⁻¹ attenuated alanine transaminase (ALT) by 28.92%, against 33.36% when 500 mg kg⁻¹ was given. A similar trend was observed in aspartate aminotransferase (AST), where 19.44% was recorded for BNSE at 250 mg kg⁻¹ and 34.93% for BNSE at 500 mg kg⁻¹. Higher efficiency was noticed for BNSE at 250 and 500 mg kg⁻¹ regarding alkaline phosphatase (ALP). An improvement of 38.73% for BNSE at 500 mg kg⁻¹ was shown. The best treatment was BNSE at 500 mg kg⁻¹, as it markedly improved liver function, such as total bilirubin (T.B.), in a dose-dependent manner. The administration of BNSE attenuated the total protein (T.P.), albumin, and globulin levels to be close to or higher than the typical values in NR rats. Conclusions: BNSE might be used for its promising hypolipidemic, hepatoprotective, and nephroprotective potential and to prevent diseases related to oxidative stress. Further research on its application in humans is highly recommended. Full article

Background: Acute pancreatitis (AP) can be life-threatening with unpredictable severity. Despite advances in management, its pathogenesis remains unclear. This study investigated metabolites and lipoprotein profiles in AP patients of African descent to understand the underlying pathophysiological conditions so as to inform prognosis and management. Methods: Serum samples were collected from 9 healthy controls (HCs) and 30 AP patients (8 with mild AP, 14 with moderately severe AP, and 8 with severe AP) on days 1, 3, 5, and 7 post epigastric pain and subjected to nuclear magnetic resonance (NMR) spectroscopy. Wilcoxon and Kruskal–Wallis rank-sum tests compared numerical covariates. Lipoprotein characterization was performed using the Liposcale test, and Spearman’s rank test assessed data correlations. The p-values < 0.05 indicated significance. Results: Thirty-eight metabolic signals and information on lipoprotein subclasses were identified from the NMR spectra. The severity of AP correlated with increased levels of 3-hydroxybutyrate and acetoacetate and decreased levels of ascorbate. Distinct metabolic phenotypes were identified and characterized by unique inflammatory and lipoprotein profiles. High-density lipoprotein cholesterol (HDL-C) decreased across all the metabolic phenotypes of AP when compared with the HC, while elevated immediate density lipoprotein cholesterol (IDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels were observed. Time-dependent changes in metabolites were indicative of responsiveness to therapy. Conclusions: Our findings indicate that dysregulated metabolites and lipoproteins can be used to differentiate AP disease state and severity. Furthermore, integrating clinical parameters with data on metabolic and lipoprotein perturbations can contribute to a better understanding of the complex pathophysiology of AP. Full article

Transportation, an unavoidable process in livestock farming, causes metabolic disorders in the body, which then lead to endocrine disruption, being immunocompromised, and growth suppression. Lipid metabolism dysregulation is a critical phenotype induced by transportation. The liver is a vital organ in lipid metabolism, with a role in both lipid synthesis and lipolysis. However, the specific mechanisms by which transportation affects hepatic lipid metabolism remain unclear. This study employed rats as a model to investigate the effects of transportation on hepatic lipid metabolism. Rats subjected to transportation showed altered serum lipid profiles, including decreased serum triglyceride (TG), low-density lipoprotein cholesterol (VLDL-C), and non-esterified fatty acid (NEFA) immediately after transportation (IAT) and serum total cholesterol (TC) on day 3, and increasing serum TG, TC, and low-density lipoprotein cholesterol (LDL-C) on day 10. Meanwhile, fatty droplets in the liver were also reduced at IAT and increased on days 3 and 10. Notably, transportation also affected hepatic-lipid-metabolism-related enzyme activities and signaling pathways, such as increased AMP-activated protein kinase alpha (AMPKα) phosphorylation and modulations in key proteins and genes related to lipid metabolism, decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) activities at IAT, and increased carnitine palmitoyl transferase 1 alpha (CPT-1α) at IAT and ACC and CPT-1α activities on days 3 and 10. Supplementation with alkaline mineral complex water (AMC) before and after transportation mitigated the adverse effects on hepatic lipid metabolism by modulating the AMPKα-SREBP-1c/PPARα pathway, enhancing lipid synthesis, and reducing the oxidative catabolism of fatty acids. AMC inhibited the transportation-induced activation of AMPKα and restored the balance of lipid-metabolism-related enzymes and pathways. These findings highlight AMC’s potential as a therapeutic intervention to alleviate transportation-induced lipid metabolism disorders, offering significant implications for improving animal welfare and reducing economic losses in livestock farming. Full article

Background/Objectives: Dyslipidemia is frequently linked to various disorders, and its clinical relevance is now recognized. The role of inflammation and oxidative stress (OS) in dyslipidemia has been acknowledged. This study assessed the potential of arbutin (ARB) to prevent dyslipidemia and its associated OS and inflammation in rats with acute hyperlipidemia. Methods: Rats received ARB orally for 14 days and a single intraperitoneal injection of poloxamer-407 on day 15. Results: Poloxamer-407 elevated circulating cholesterol (CHOL), triglycerides (TG), very low-density lipoprotein (vLDL), and LDL, and reduced high-density lipoprotein (HDL)-C and lipoprotein lipase (LPL). ARB ameliorated the circulating lipids and LPL, and suppressed 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in rat liver and in vitro. Fatty acid synthase (FAS) in rat liver and its in vitro activity were suppressed by ARB, which also upregulated the LDL receptor (LDL-R) and ABCA1, and had no effect on ABCG5 and ABCG8 mRNA. ARB ameliorated liver malondialdehyde and nitric oxide and enhanced antioxidants in rats with dyslipidemia. Liver NF-κB p65 and blood inflammatory cytokines were increased in dyslipidemic rats, effects that were reversed by ARB. Moreover, ARB effectively suppressed lymphocyte E-NTPDase and E-ADA activities in dyslipidemic rats. The biochemical findings were supported by in silico data showing the affinity of ARB to bind LDL-R PCSK9 binding domain, HMGCR, FAS, and E-NTPDase. Conclusions: ARB possessed anti-dyslipidemia, anti-inflammatory, and antioxidant effects mediated via the modulation of CHOL and TG synthesis, LPL, lymphocyte E-NTPDase and E-ADA, and cytokine release in rats. Thus, ARB could be an effective agent to attenuate dyslipidemia and its associated OS and inflammation, pending further studies as well as clinical trials. Full article