Triacylglycerol Levels Research Articles

Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study.

Endometriosis is a prevalent chronic inflammatory disease characterized by a considerable delay between initial symptoms and diagnosis through surgery. The pressing need for a timely, non-invasive diagnostic solution underscores the focus of current research efforts. This study examines the diagnostic potential of the menstrual blood lipidome. The lipid profile of 39 samples (23 women with endometriosis and 16 patients in a control group) was acquired using reverse-phase high-performance liquid chromatography-mass spectrometry with LipidMatch processing and identification. Profiles were normalized based on total ion counts. Significant differences in lipids were determined using the Mann-Whitney test. Lipids for the diagnostic model, based on logistic regression, were selected using a combination of variance importance projection filters and Akaike information criteria. Levels of ceramides, sphingomyelins, cardiolipins, triacylglycerols, acyl- and alkenyl-phosphatidylethanolamines, and alkenyl-phosphatidylcholines increased, while acyl- and alkyl-phosphatidylcholines decreased in cases of endometriosis. Plasmenylphosphatidylethanolamine PE P-16:0/18:1 and cardiolipin CL 16:0_18:0_22:5_22:6 serve as marker lipids in the diagnostic model, exhibiting a sensitivity of 81% and specificity of 85%. The diagnostic approach based on dried spots of menstrual blood holds promise as an alternative to traditional non-invasive methods for endometriosis screening.

Phospholipid and glycerolipid metabolism as potential diagnostic biomarkers for acute pancreatitis

BackgroundAcute pancreatitis (AP) is characterized as a systemic inflammatory condition posing challenges in diagnosis and prognosis assessment. Lipid metabolism abnormalities, especially triacylglycerol (TAG) levels, have been reported, indicating their potential as biomarkers in acute pancreatitis. However, the performance of the TAG cycle, including phospholipid and glycerolipid metabolism, in AP patients has not yet been reported.MethodsThis study enrolled 91 patients with acute biliary pancreatitis (ABP), 27 with hyperlipidaemic acute pancreatitis (HLAP), and 58 healthy controls (HCs), and their plasma phospholipid and glycerolipid levels were analyzed through liquid chromatography‒mass spectrometry. The phospholipid and glycerolipid contents of plasma collected from AP patients on the first, third, and seventh days of hospitalization were also measured. An orthogonal partial least squares discriminant analysis model served to differentiate the ABP, HLAP and HC groups, and potentially diagnostic lipids were evaluated via receiver operating characteristic curves in both the test and validation sets. Correlations between clinical data and lipids were conducted using Spearman’s method. Clustering via the ‘mfuzz’ R package and the Kruskal‒Wallis H test were conducted to monitor changes during hospitalization.ResultsCompared with those in HCs, the levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidic acid (PA) were lower in AP patients, whereas the levels of phosphatidylinositol (PI) and phosphatidylglycerol (PG) showed the opposite trend. Interestingly, TAG levels were positively correlated with white blood cell counts in ABP patients, and TAGs containing 44–55 carbon atoms were highly correlated with plasma TAG levels in HLAP patients. Phospholipid levels exhibited an inverse correlation with AP markers, in contrast to glycerolipids, which demonstrated a positive correlation with these markers. Additionally, PE (O-16:0/20:4) and PE (18:0/22:6) emerged as potential biomarkers because of their ability to distinguish ABP and HLAP patients from HCs, showing area under the curve (AUC) values of 0.932 and 0.962, respectively. PG (16:0/18:2), PG (16:0/20:4), PE (P-16:0/20:2), PE (P-18:2/18:2), PE (P-18:1/20:3), PE (P-18:1/20:4), PE (O-16:0/20:4), and TAG (56:6/FA18:0) were significantly changed in ABP patients who improved. For HLAP patients, PC (18:0/20:3), TAG (48:3/FA18:1), PE (P-18:0/16:0), and TAG (48:4/FA18:2) showed different trends in patients with improvement and deterioration, which might be used for prognosis.ConclusionsPhospholipids and glycerolipids were found to be potential biomarkers in acute pancreatitis, which offers new diagnostic and therapeutic insights into this disease.

Role of metabolites in mediating the effect of triacylglycerol on aplastic anemia

ABSTRACT Background Observational studies have found a link between lipid metabolism disorders and aplastic anemia (AA). However, due to confounding variables and reverse causation, it is difficult to conclude such a causal link. The precise mechanism and potential implications of lipid metabolism disorder in AA remain unclear, necessitating further studies in this area. Method This study aimed to examine the causal relationship between 38 different subtypes of triacylglycerols and AA using two-sample Mendelian randomization (MR). Additionally, two-step MR analyses were conducted to investigate the mediating effects of vitamin A to oleoyl-linoleoyl-glycerol (18:1–18:2) ratio. Results MR analysis showed that triacylglycerol (53:3) levels were positively associated with the risk of AA [inverse variance weighting (IVW): odds ratio (OR) = 1.131,95% confidence interval (CI):1.029-1.243, P = 0.011; Bayesian weighted MR (BWMR): OR = 1.137,95% CI:1.031-1.254, P = 0.010]. Triacylglycerol (53:3) level showed no inverse causality with AA (IVW:P = 0.834; BWMR:P = 0.349). Mediation analyses showed that increasing the vitamin A to oleoyl-linoleoyl-glycerol (18:1–18:2) ratio can decrease the risk of AA. Conclusion This study revealed the association between vitamin A to oleoyl-linoleoyl-glycerol (18:1–18:2) ratio, triacylglycerol (53:3) levels and AA, and indicated that lowering triacylglycerol (53:3) levels can reduce the risk of AA.

Nutriomic Effects of Precision Lipids on Murine Hepatic Triacylglycerol Alterations Induced by High-Fat Diets.

This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.

Maternal genetics and diet modulate vitamin A homeostasis of the offspring and affect the susceptibility to obesity in adulthood in mice.

Perinatal nutrition exerts a profound influence on adult metabolic health. This study aimed to investigate whether increased maternal vitamin A (VA) supply can lead to beneficial metabolic phenotypes in the offspring. The researchers utilized mice deficient in the intestine-specific homeobox (ISX) transcription factor, which exhibits increased intestinal VA retinoid production from dietary β-carotene (BC). ISX-deficient dams were fed a VA-sufficient or a BC-enriched diet during the last week of gestation and the whole lactation period. Total retinol levels in milk and weanling livers were 2- to 2.5-fold higher in the offspring of BC-fed dams (BC offspring), indicating increased VA supplies during late gestation and lactation. The corresponding VA-sufficient and BC offspring (males and females) were compared at weaning and adulthood after being fed either a standard or high-fat diet (HFD) with regular VA content for 13 weeks from weaning. HFD-induced increases in adiposity metrics, such as fat depot mass and adipocyte diameter, were more pronounced in males than females and were attenuated or suppressed in the BC offspring. Notably, the BC offspring were protected from HFD-induced increases in circulating triacylglycerol levels and hepatic steatosis. These protective effects were associated with reduced food efficiency, enhanced capacity for thermogenesis and mitochondrial oxidative metabolism in adipose tissues, and increased adipocyte hyperplasia rather than hypertrophy in the BC offspring. In conclusion, maternal VA nutrition influenced by genetics may confer metabolic benefits to the offspring, with mild increases in late gestation and lactation protecting against obesity and metabolic dysregulation in adulthood.NEW & NOTEWORTHY A genetic mouse model, deficient in intestine-specific homeobox (ISX) transcription factor, is used to show that a mildly increased maternal vitamin A supply from β-carotene feeding during late gestation and lactation programs energy and lipid metabolism in tissues and protects the offspring from diet-induced hypertrophic obesity and hepatic steatosis. This knowledge may have implications for human populations where polymorphisms in ISX and ISX target genes involved in vitamin A homeostasis are prevalent.

Dietary medium-chain fatty acids reduce hepatic fat accumulation via activation of a CREBH-FGF21 axis

ObjectiveDietary medium-chain fatty acids (MCFAs), characterized by chain lengths of 8–12 carbon atoms, have been proposed to have beneficial effects on glucose and lipid metabolism, yet the underlying mechanisms remain elusive. We hypothesized that MCFA intake benefits metabolic health by inducing the release of hormone-like factors. MethodsThe effects of chow diet, high-fat diet rich in long-chain fatty acids (LCFA HFD) fed ad libitum or pair-fed to a high-fat diet rich in MCFA (MCFA HFD) on glycemia, hepatic gene expression, circulating fibroblast growth factor 21 (FGF21), and liver fat content in both wildtype and Fgf21 knockout mice were investigated. The impact of a single oral dose of an MCFA-rich oil on circulating FGF21 and hepatic Fgf21 mRNA expression was assessed. In flag-tagged Crebh knockin mice and liver-specific Crebh knockout mice, fed LCFA HFD or MCFA HFD, active hepatic CREBH and hepatic Fgf21 mRNA abundance were determined, respectively. ResultsMCFA HFD improves glucose tolerance, enhances glucose clearance into brown adipose tissue, and prevents high-fat diet-induced hepatic steatosis in wildtype mice. These benefits are associated with increased liver expression of CREBH target genes (Apoa4 and Apoc2), including Fgf21. Both acute and chronic intake of dietary MCFAs elevate circulating FGF21. Augmented hepatic Fgf21 mRNA following MCFA HFD intake is accompanied by higher levels of active hepatic CREBH; and MCFA-induced hepatic Fgf21 expression is blocked in mice lacking Crebh. Notably, while feeding male and female Fgf21 wildtype mice MCFA HFD results in reduced liver triacylglycerol (TG) levels, this liver TG-lowering effect is blunted in Fgf21 knockout mice fed MCFA HFD. The reduction in liver TG levels observed with MCFA HFD was independent of weight loss. ConclusionsDietary MCFAs reduce liver fat accumulation via activation of a CREBH-FGF21 signaling axis.

Zinc finger 259 gene polymorphisms in Egyptian patients with metabolic syndrome and its association with dyslipidemia.

Zinc finger protein 1 (ZPR1), encoded by the ZNF259 gene, plays crucial roles in transcriptional regulation and cell cycle progression. Despite its known functions, its specific involvement in Metabolic Syndrome (MetS) remains debated. Genome-wide association studies have identified several genes, including ZNF259, implicated in lipid metabolism and associated with MetS. Single nucleotide polymorphisms (SNPs) in ZNF259 have been linked to altered lipid metabolism during the development of MetS. This study aims to investigate the association between MetS in Egyptian patients and three specific ZNF259 SNPs: rs964184, rs2075294, and rs2075290. The objective is to explore how these SNPs correlate with MetS development, other health outcomes, and their interaction with dyslipidemia biomarkers. 200 Egyptian participants were enrolled, and divided into two groups: 100 patients diagnosed with dyslipidemia and 100 healthy controls. The study involved comprehensive assessments, including lipid profile analysis, anthropometric measurements, and genotyping of rs964184, rs2075290, and rs2075294 in the ZNF259 gene using Real-Time Polymerase Chain Reaction (PCR). The findings indicate that rs964184 SNP correlates significantly with elevated plasma triacylglycerol (TG) levels, while rs2075290 and rs2075294 are associated with higher total serum cholesterol (TC) and TG levels. Among these SNPs, rs2075294 showed the highest predictive value (area under the curve of 0.748), followed by rs2075290 (0.738), and rs964184 (0.583), suggesting rs2075294 as the most influential SNP in MetS prediction. This study underscores the predictive role of ZNF259 SNPs in MetS risk among Egyptians. Future research should further explore the implications of ZNF259 in MetS pathogenesis and its potential as a biomarker for personalized health interventions.

Diacylglycerides as nutrition components or precursors of carcinogens: a critical view on an ambular question

Obesity is considered as a noninfectious epidemic worldwide. Metabolic disorders associated with the accumulation of adipose tissue lead to obesity-associated diabetes mellitus and cardiovascular diseases. Diet is a component of treatment of diseases associated with obesity. The most commonly used diets are caloric restriction by reducing fat in the diet. Over the years, there have been several attempts to use diacylglycerol (DAG) as components of dietary oils owing to its ability to suppress the accumulation of visceral fat and reduce postprandial levels of triacylglycerol and cholesterol and glucose in the blood serum. However, in 2009, it was found that when oil was processed at high temperatures during physical refining, DAG-enriched oil had the highest levels of potentially harmful glycidyl esters compared to conventional refined fats and oils. The study of the negative effects of glycidyl esters has prompted the food industry, which has traditionally used oil, to focus on strategies in preventing or mitigating these effects by changing the refining process or modifying deodorization equipment to reduce or eliminate process contaminants.

Increased secretion of adipocyte-derived extracellular vesicles is associated with adipose tissue inflammation and the mobilization of excess lipid in human obesity

BackgroundObesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesity’s impact on EV secretion from human AT remains limited.MethodsWe investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography–mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry.ResultsEVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation.ConclusionsWe are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.

Metformin Lowers Plasma Triacylglycerol Levels in Mice with Impaired Carnitine Biosynthesis and Fatty Liver

The antidiabetic drug metformin has a wide range of metabolic effects and may also reduce the risk of obesity-related diseases. The aim of the current study was to investigate if metformin could counteract meldonium-induced fatty liver. Four groups of male C57BL/6J mice were fed a low-fat control diet, or low-fat diets supplemented with metformin, meldonium, or metformin and meldonium for three weeks. Meldonium treatment led to 5.2-fold higher hepatic triacylglycerol (TAG) levels compared to control, and metformin lowered the meldonium-induced lipid accumulation insignificantly by 21%. Mice treated with metformin and meldonium demonstrated significantly lower weight gain, visceral adipose tissue weight and plasma levels of TAG compared to meldonium alone. The hepatic mRNA level of carnitine palmitoyl transferase 1 was increased 2-fold with combined meldonium and metformin treatment compared to meldonium treatment (p < 0.001). Increased hepatic expression of genes involved in fatty acid oxidation and lipid transport was observed in the combination group compared to control, and increased gene expression of the mitochondrial uncoupling protein UCP2 was observed compared to the meldonium group. In addition, the product of fatty acid oxidation, acetylcarnitine, increased in plasma in metformin-treated mice. Altogether, metformin treatment influenced hepatic lipid metabolism and lowered plasma TAG in meldonium-induced fatty liver in mice.

Prolonged Cold Exposure Negatively Impacts Atlantic Salmon (Salmo salar) Liver Metabolism and Function.

Large-scale mortality events have occurred during the winter in Atlantic salmon sea cages in Eastern Canada and Iceland. Thus, in salmon held at 3 °C that were apparently healthy (i.e., asymptomatic) and that had 'early' and 'advanced' symptoms of 'winter syndrome'/'winter disease' (WS/WD), we measured hepatic lipid classes and fatty acid levels, and the transcript expression of 34 molecular markers of fatty liver disease (FLD; a clinical sign of WS/WD). In addition, we correlated our results with previously reported characteristics associated with this disease's progression in these same individuals. Total lipid and triacylglycerol (TAG) levels increased by ~50%, and the expression of 32 of the 34 genes was dysregulated, in fish with symptoms of FLD. TAG was positively correlated with markers of inflammation (5loxa, saa5), hepatosomatic index (HSI), and plasma aspartate aminotransferase levels, but negatively correlated with genes related to lipid metabolism (elovl5b, fabp3a, cd36c), oxidative stress (catc), and growth (igf1). Multivariate analyses clearly showed that the three groups of fish were different, and that saa5 was the largest contributor to differences. Our results provide a number of biomarkers for FLD in salmon, and very strong evidence that prolonged cold exposure can trigger FLD in this ecologically and economically important species.

Circulating Lipid Profiles Associated With Resistance to Androgen Deprivation Therapy in Localized Prostate Cancer.

Intense androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPIs) before radical prostatectomy (RP) produced favorable pathologic responses in approximately 20% of patients. The molecular reason for the low rate of response remains unclear. Lipid metabolism is known to influence androgen receptor signaling and ARPI efficacy. The aim of the study was to identify circulating lipid profiles associated with ADT/ARPI resistance in localized prostate cancer. Two independent experimental approaches were used. Experiment 1: Post hoc analysis of the association between plasma lipidomic profiles and ADT/ARPI response was performed on patients (n = 104) from two phase II trials of neoadjuvant ADT/ARPI. Response to ADT/ARPI was defined by pathologic response. Experiment 2: Patient-derived tumor explants from RP (n = 105) were cultured in enzalutamide for 48 hours. Explant response to enzalutamide was evaluated against pre-RP plasma lipidomic profiles (n = 105) and prostate tissue lipidomic profiles (n = 36). Response was defined by Ki67 (cell proliferation marker) fold difference between enzalutamide and vehicle-treated explants. In both experiments, associations between lipid profiles and ADT/ARPI response were analyzed by latent class analysis. Pretreatment plasma lipid profiles classified each experimental cohort into two groups with differences in ADT/ARPI response rates. The response rates of the groups were 9.6% versus 29% in experiment 1 (chi-squared test P = .012) and 49% versus 70% in experiment 2 (chi-squared test P = .037). In both experiments, the group with a higher incidence of ADT/ARPI resistance had higher plasma levels of sphingomyelin, glycosylceramides, free fatty acids, acylcarnitines, cholesterol esters, and alkyl/alkenyl-phosphatidylcholine and lower plasma levels of triacylglycerols, diacylglycerols, and phosphoethanolamine (t-test P < .05). Pretreatment circulating lipid profiles are associated with ADT/ARPI resistance in localized cancer in both human cohorts and explant models.

The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease.

Glomerular lipid accumulation is a defining feature of diabetic kidney disease (DKD); however, the precise underlying mechanism requires further elucidation. Recent evidence suggests a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in intracellular lipid homeostasis. Although PCSK9 is present in kidneys, its role within kidney cells and relevance to renal diseases remain largely unexplored. Therefore, we investigated the role of intracellular PCSK9 in regulating lipid accumulation and homeostasis in the glomeruli and podocytes under diabetic conditions. Furthermore, we aimed to identify the pathophysiological mechanisms responsible for the podocyte injury that is associated with intracellular PCSK9-induced lipid accumulation in DKD. In this study, glomeruli were isolated from human kidney biopsy tissues, and glomerular gene-expression analysis was performed. Also, db/db and db/m mice were used to perform glomerular gene-expression profiling. We generated DKD models using a high-fat diet and low-dose intraperitoneal streptozocin injection in C57BL/6 and Pcsk9 knockout (KO) mice. We analysed cholesterol and triacylglycerol levels within the kidney cortex. Lipid droplets were evaluated using BODIPY staining. We induced upregulation and downregulation of PCSK9 expression in conditionally immortalised mouse podocytes using lentivirus and siRNA transfection techniques, respectively, under diabetic conditions. A significant reduction in transcription level of PCSK9 was observed in glomeruli of individuals with DKD. PCSK9 expression was also reduced in podocytes of animals under diabetic conditions. We observed significantly higher lipid accumulation in kidney tissues of Pcsk9 KO DKD mice compared with wild-type (WT) DKD mice. Additionally, Pcsk9 KO mouse models of DKD exhibited a significant reduction in mitochondria number vs WT models, coupled with a significant increase in mitochondrial size. Moreover, albuminuria and podocyte foot process effacement were observed in WT and Pcsk9 KO DKD mice, with KO DKD mice displaying more pronounced manifestations. Immortalised mouse podocytes exposed to diabetic stimuli exhibited heightened intracellular lipid accumulation, mitochondrial injury and apoptosis, which were ameliorated by Pcsk9 overexpression and aggravated by Pcsk9 knockdown in mouse podocytes. The downregulation of PCSK9 in podocytes is associated with lipid accumulation, which leads to mitochondrial dysfunction, cell apoptosis and renal injury. This study sheds new light on the potential involvement of PCSK9 in the pathophysiology of glomerular lipid accumulation and podocyte injury in DKD.

Chlorogenic Acid and its Isomers Attenuate NAFLD by Mitigating Lipid Accumulation in Oleic Acid-Induced HepG2 Cells and High-Fat Diet- Fed Zebrafish.

Chlorogenic acid (Chl), isochlorogenic acid A (Isochl A), and isochlorogenic acid B (Isochl B) are naturally occurring phenolic compounds, which have been shown to exert a regulatory effect on lipid metabolism. However, the mechanism underlying this effect remains unclear. Herein, we investigated the inhibitory effects and underlying mechanisms of these three phenolic compounds on oleic acid (OA)-induced HepG2 cells and high-fat diet (HFD)-fed zebrafish. Lipid accumulation and triacylglycerol levels increased in OA-induced cells, which was attenuated by Chl, Isochl A, and Isochl B. Moreover, the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) decreased, while superoxide dismutase (SOD) levels increased by Chl, Isochl A and Isochl B treatment. Western blot analysis demonstrated that Chl, Isochl A and Isochl B reduced the expression of lipogenesis-related protein, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, peroxisome proliferator-activated receptor alpha gamma (PPARα) was increased by Chl, Isochl A, and Isochl B treatment. In addition, our results indicated that Chl, Isochl A and Isochl B decreased lipid profiles and lipid accumulation in HFD-fed zebrafish. Thus, these findings highlight the potential of Chl, Isochl A, and Isochl B as effective agents for treating or/and ameliorating non-alcoholic fatty liver disease (NAFLD).

Antihyperlipidemic activity of myricetin

AbstractMyricetin has been reported to have a wide variety of beneficial physiological functions. The present study investigated the antihyperlipidaemic activity of myricetin against hyperlipidaemia of high-fat diet-fed obese rats. The four-week antihyperlipidaemic activity was assayed by giving different doses of myricetin to hyperlipidaemic rats. Results showed that myricetin could reduce the harm caused by oxidative stress, decrease thiobarbituric acid reactive substances value, and decrease total cholesterol and triacylglycerol levels of hyperlipidaemic rats. Quantitative analysis of gene expression showed that myricetin's lipid-lowering activity can be activated by downregulating gene expression of fatty acid synthase (FAS) and peroxisome proliferator-activated receptor-γ (PPARγ) with upregulation of hormone-sensitive lipase (HSL) mRNA level. Thus, myricetin had significant health benefits and could be explored as a potentially promising dietary supplement for treating hyperlipidaemia.

Liposomes have a direct effect on multiple myeloma: a Mendelian randomization study.

Multiple myeloma (MM), a malignant disease of plasma cells originating in the bone marrow, is influenced significantly by genetic factors. Although plasma liposomes have been linked to MM, the nature of their potential causal relationship remains to be elucidated. This study aims to explore this relationship using Mendelian randomization (MR) analysis. Liposome-associated genetic instrumental variables (IVs) were identified from plasma lipidomics data of 7,174 Finnish individuals within a Genome-Wide Association Study (GWAS) pooled database. A MM pooled dataset was sourced from a GWAS meta-analysis encompassing 150,797 individuals, including 598 MM patients and 218,194 controls. These IVs underwent MR analysis, adhering to strict criteria for correlation, independence, and the exclusion of confounders. The inverse variance weighted (IVW) method, MR-Egger method, weighted median (WM) method, and simple median were utilized for MR analysis assessment, alongside Cochran's Q test, MR-Egger intercept, MR-Pleiotropy Residual Sum and Outlier (MR-RESSO) method, and leave-one-out analysis for evaluating heterogeneity, multiplicity, and instrumental bias. The study identified 88 significant, independent single nucleotide polymorphisms (SNPs) as IVs for MR analysis, each with an F-statistic value above 10, indicating robustness against weak instrument bias. IVW analysis revealed associations between six plasma liposome components and MM risk (p < 0.05). Phosphatidylinositol (16:0_18:1) serum levels (odds ratio [OR] = 1.769, 95% confidence interval [CI]: 1.132-2.763, p = 0.012) and triacylglycerol (56:4) levels (p = 0.026, OR = 1.417, 95% CI: 1.042-1.926) were positively correlated with the risk of multiple myeloma development. Phosphatidylethanolamine (18:0_20:4) (p = 0.004, 95% CI: 0.621-0.916, OR = 0.754), phosphatidylcholine (18:2_20:4) (p = 0.004, OR = 0.680, 95% CI: 0.519-0.889), sterol ester (27:1/18:3) levels (p = 0.013, OR = 0.677, 95% CI: 0.498-0.922), and phosphatidylcholine (O-18:2_20:4) levels (OR = 0.710, 95% CI: 0.517-0.913, p = 0.033) were negatively associated with the risk of developing multiple myeloma. The Cochran's Q test did not detect statistical method heterogeneity, nor did the MR-RESSO test or the MR-Egger intercept detect horizontal pleiotropy; leave-one-out analyses confirmed the absence of bias from individual SNPs. Our findings suggest a complex relationship between plasma liposome components and MM risk. Elevated serum levels of triacylglycerol and phosphatidylinositol are positively associated with MM risk, while certain phospholipids and sterol esters offer a protective effect. This study provides valuable insights into the clinical relevance of liposomes in the pathology of multiple myeloma.

Legacy and alternative per- and polyfluoroalkyl substances (PFAS) alter the lipid profile of HepaRG cells

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various industrial and consumer products. They have gained attention due to their ubiquitous occurrence in the environment and potential for adverse effects on human health, often linked to immune suppression, hepatotoxicity, and altered cholesterol metabolism. This study aimed to explore the impact of ten individual PFAS, 3 H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP/Adona), ammonium perfluoro-(2-methyl-3-oxahexanoate) (HFPO-DA/GenX), perfluorobutanoic acid (PFBA), perfluorobutanesulfonic acid (PFBS), perfluorodecanoic acid (PFDA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS) on the lipid metabolism in human hepatocyte-like cells (HepaRG). These cells were exposed to different concentrations of PFAS ranging from 10 µM to 5000 µM. Lipids were extracted and analyzed using liquid chromatography coupled with mass spectrometry (LC- MS-QTOF). PFOS at 10 µM and PFOA at 25 µM increased the levels of ceramide (Cer), diacylglycerol (DAG), N-acylethanolamine (NAE), phosphatidylcholine (PC), and triacylglycerol (TAG) lipids, while PMPP/Adona, HFPO-DA/GenX, PFBA, PFBS, PFHxA, and PFHxS decreased the levels of these lipids. Furthermore, PFOA and PFOS markedly reduced the levels of palmitic acid (FA 16.0). The present study shows distinct concentration-dependent effects of PFAS on various lipid species, shedding light on the implications of PFAS for essential cellular functions. Our study revealed that the investigated legacy PFAS (PFOS, PFOA, PFBA, PFDA, PFHxA, PFHxS, and PFNA) and alternative PFAS (PMPP/Adona, HFPO-DA/GenX and PFBS) can potentially disrupt lipid homeostasis and metabolism in hepatic cells. This research offers a comprehensive insight into the impacts of legacy and alternative PFAS on lipid composition in HepaRG cells.

Dyslipidemia and ANGPTL8 evaluation in young females with Type 1 diabetes mellitus.

ANGPTL8, commonly referred to as betatrophin, has demonstrated promise as a dependable marker for the onset of complications associated with diabetes mellitus, such as dyslipidemia. The objective of this study is to evaluate the lipid profile and ANGPTL8 levels in people diagnosed with Type 1 Diabetes Mellitus (T1DM). A retrospective case-control study was performed on a group of 100 adolescent females, aged 13-17 years. This group consisted of individuals diagnosed with T1DM from the Diabetes and Endocrine Department at Medina's King Fahad Hospital in Saudi Arabia. Additionally, 100 healthy adolescent females of the same age range were included as controls. The hospital conducted laboratory studies to evaluate glucose, HbA1c, insulin, and lipid profiles. The ANGPTL8 levels were quantified using Enzyme-Linked Immunosorbent Assay (ELISA). Patients with T1DM had ANGPTL8 levels that were twice as high as those observed in individuals without any health conditions. The two groups had contrasting levels of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), C-peptides, triacylglycerol (TG), and cholesterol, along with elevated Atherogenic Index of Plasma readings. Diabetes mellitus patients had considerably elevated values compared to the control group. There was a significant correlation between ANGPTL8 concentrations and lipid abnormalities, with P-values less than 0.05. 56% of the 100 patients exhibited dyslipidemia. The research found a correlation between dyslipidemia and elevated levels of ANGPTL8 in diabetic patients. The concentration of ANGPTL8 had a positive correlation with glucose, HbA1c, TG, and C-peptides while displaying a negative correlation with high-density lipoprotein cholesterol (HDL-C). ANGPTL8 levels were found to be elevated in Saudi young women who were diagnosed with TIDM. ANGPTL8 may potentially contribute to dyslipidemia in individuals with T1DM, hence increasing the susceptibility to cardiovascular disease (CVD). Therefore, ANGPTL8 has the potential to impact lipid metabolism, namely Triglycerides, as a biological route. The results highlight the need to analyze lipid profiles and do ANGPTL8 testing in young females diagnosed with T1DM at an early stage to prevent complications.

Effect of radio frequency roasting on the lipid profile of peanut oil and the mechanism of lipids transformation: Revealed by untargeted lipidomics approach

Radio frequency (RF) heating has been proved an alternative roasting method for peanuts, which could effectively degrade aflatoxins and possesses the advantages of greater heating efficiency and penetration depth. This study aimed to investigate the influences of RF roasting on the lipid profile of peanut oil under 150 °C target temperature with varied peanut moisture contents (8.29 % and 20 %) and holding times (0, 7.5, and 15 min), using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based lipidomics. In total, 2587 lipid species from 35 subclasses were identified. After roasting, the contents of sterol lipid (ST) and subclasses of glycerophospholipids (GPs) and glycoglycerolipids increased significantly, while fatty acid (FA), Oxidized (Ox-) FA, cholesterol (CE), and all subclasses of glycerolipids (GLs) decreased, and 1084 differential lipids were screened. The highest ST and lowest CE contents in peanut oil were achieved by medium roasting (7.5 min). The raise in moisture content of peanut simply affected a few GPs subclasses adversely. Compared with hot air (HA) roasting, RF decelerated lipid oxidation, showing higher levels of diacylglycerol, triacylglycerol and FA, with no additional negative impact and only 69 exclusive differential lipids. During RF roasting, hydrolysis and oxidation of fatty acyl chains into secondary oxides were the central behaviors of lipids transformation. This study could provide insights into the lipid changes and transformation mechanism of peanut oil by RF roasting processing.

Butein derivatives prevent obesity and improve insulin resistance through the induction of energy expenditure in high-fat diet-fed obese mice

Obesity is a global public health problem and is related with fatal diseases such as cancer and cardiovascular and metabolic diseases. Medical and lifestyle-related strategies to combat obesity have their limitations. White adipose tissue (WAT) browning is a promising strategy for increasing energy expenditure in individuals with obesity. Uncoupling protein 1 (UCP1) drives WAT browning. We previously screened natural products that enable induction of Ucp1 and demonstrated that these natural products induced WAT browning and increased energy expenditure in mice with diet-induced obesity. In this study, we aimed to extensively optimise the structure of compound 1, previously shown to promote WAT browning. Compound 3 s exhibited a significantly higher ability to induce Ucp1 in white and brown adipocytes than did compound 1. A daily injection of compound 3 s at 5 mg/kg prevented weight gain by 13.6 % in high-fat diet–fed mice without any toxicological observation. In addition, compound 3 s significantly improved glucose homeostasis, decreased serum triacylglycerol levels, and reduced total cholesterol and LDL cholesterol levels, without altering dietary intake or physical activity. Pharmaceutical properties such as solubility, lipophilicity, and membrane permeability as well as metabolic stability, half-life (T1/2), and blood exposure ratio of i.p to i.v were significantly improved in compound 3 s when compared with those in compound 1. Regarding the mode of action of WAT browning, the induction of Ucp1 and Prdm4 by compounds 1 and 3 s was dependent on Akt1 in mouse embryonic fibroblasts. Therefore, this study suggests the potential of compound 3 s as a therapeutic agent for individuals with obesity and related metabolic diseases, which acts through the induction of WAT browning as well as brown adipose tissue activation.