Disturbances In Lipid Metabolism Research Articles

Salsalate and/or metformin therapy confer beneficial metabolic effects in olanzapine treated female mice

Antipsychotic medications are used in the management of schizophrenia and a growing number of off-label conditions. While effective at reducing psychoses, these drugs possess noted metabolic side effects including weight gain, liver lipid accumulation and disturbances in glucose and lipid metabolism. To counter the side effects of antipsychotics standard of care has typically included metformin. Unfortunately, metformin does not protect against antipsychotic induced metabolic disturbances in all patients and thus additional treatment approaches are needed. One potential candidate could be salsalate, the prodrug of salicylate, which acts synergistically with metformin to improve indices of glucose and lipid metabolism in obese mice. The purpose of the current investigation was to compare the effects of salsalate, metformin and a combination of both drugs, on weight gain and indices of metabolic health in female mice treated with the antipsychotic, olanzapine. Herein we demonstrate that salsalate was equally as effective as metformin in protecting against olanzapine induced weight gain and liver lipid accumulation with no additional benefit of combining both drugs. Conversely, metformin treatment, either alone or in combination with salsalate, improved indices of glucose metabolism and increased energy expenditure in olanzapine treated mice. Collectively, our findings provide evidence that dual therapy with both metformin and salsalate could be an efficacious approach with which to dampen the metabolic consequences of antipsychotic medications.

The Effects of Resveratrol Supplementation on the Metabolism of Lipids in Metabolic Disorders.

Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.

Beneficial effects of silibinin on serum lipids, bile acids, and gut microbiota in methionine-choline-deficient diet-induced mice.

Silibinin (SIL) is a flavonoid lignin isolated from the fruit and seeds of silybum marianum that exhibits good therapeutic potential for NASH. However, the effects of SIL on serum lipids, bile acids (BAs), and gut microbiota (GM) in NASH mice remain unknown. The present work aimed to explore the beneficial effects of SIL supplementation on serum lipids, bile acids, and gut microbiota in MCD mice. After male C57BL/6 mice were fed with a methionine-choline deficient (MCD) diet and simultaneously gavaged with SIL (20 mg/kg. d) for 8 weeks, the pathological changes of liver tissue were observed by oil red O, haematoxylin-eosin, and Masson tricolor staining; the levels of serum AST and ALT, and liver TG and MDA were detected by assay kits; metabonomics and 16S rDNA sequencing were used to analyze the composition of serum lipids and BAs and the abundance of GM; and the mRNA expression levels of hepatic genes related to BAs homeostasis were detected by RT-qPCR. The results indicated that SIL treatment decreased the levels of 26 lipids (including four arachidonic acids, seven FFAs, 12 acyl carnitines, and three GPs) and two BAs (23-DCA, GLCA), while Dubosiella increased the levels of 10 lipids (including TxB3, PG16:0_18:1, Cer t18:0/24:0 and 7 TGs), five BAs (β-MCA, α-MCA, UDCA, 3-oxo-DCA and HCA), and two GMs (Verrucomicrobiota and Akkermansiaceae) of MCD mice, but had no significant effect on the mRNA expression of CYP7A1, CYP27A1, Bsep, Mrp2, Ntcp, or Oatp1b2. Therefore, influencing GM composition and then regulating the levels of serum lipids and BAs through enterohepatic axis should be an important mechanism of SIL-induced alleviative effect on MCD mice. More importantly, we found that SIL had a good coordination in regulating the abundance of GM and the contents of serum lipids and BAs in MCD mice, that is, when the abundance of probiotics was up-regulated, the content of beneficial unsaturated fatty acids in serum was up-regulated, while the serum levels of harmful lipids and BAs were down-regulated. The alleviating effect of SIL on NASH may be closely related to the correction of intestinal bacteria disorder, serum bile acid, and lipid metabolic disturbance in mice.

Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review.

Hyperlipidemia is a metabolic disorder, which is a major risk factor for atherosclerosis, stroke, and coronary heart disease. Although lipid-lowering treatments have been extensively studied, safer treatments with fewer adverse effects are needed. Rhubarb is a traditional Chinese medicine that has lipid-lowering, anti-inflammatory, and antioxidant properties. Disturbance in lipid metabolism is the basis of tissue damage caused by hyperlipidemia and plays a key role in the development of hyperlipidemia; however, the molecular mechanisms by which rhubarb regulates lipid metabolism to lower lipid levels are yet to be elucidated. We conducted this study to summarize the phytochemical constituents of Rheum officinale and provide a comprehensive review of the molecular mechanisms underlying the regulation of lipid metabolism during hyperlipidemia treatment. It was found that rhubarb extracts, including emodin, rhubarb acid, and rhubarb phenol, regulate total cholesterol, triglyceride, TNF-α, and IL-1β levels through signaling pathways such as C/EBP α, 3T3-L1, PPAR α, and AMPK, thereby improving the hyperlipidemic state. This suggests that rhubarb is a natural drug with lipid-lowering potential, and an in-depth exploration of its lipid-lowering mechanism can provide new ideas for the prevention and treatment of hyperlipidemia.

Rotundic acid alleviates hyperlipidemia in rats by regulating lipid metabolism and gut microbiota.

Disturbances in lipid metabolism and dysbiosis of the gut microbiota play an important role in the progression of hyperlipidemia. Previous study indicated that Ilicis Rotundae Cortex possesses anti-hyperlipidemic activity, and rotundic acid (RA) identified as a key active compound to be incorporated into the body. The study aimed to evaluate the anti-hyperlipidemia effects of RA and explored its impact on gut microbiota and lipid metabolism, as well as its possible mechanisms for improving hyperlipidemia. The study methodology included a comprehensive evaluation of the effects of RA on steatosis markers of hyperlipidemia, lipid metabolism, and gut microbiota by assessing biochemical parameters and histopathology, lipidomics, 16S rRNA gene sequencing, and short-chain fatty acid (SCFA) assays. The results showed that RA effectively reduced body weight and the steatosis markers in serum and liver. Moreover, the lipidomic analysis revealed significant changes in plasmatic and hepatic lipid levels, and these were restored by RA. According to the results of 16S rRNA gene sequencing, RA supplementation raised the relative abundance of Bacteroidetes and Proteobacteria while decreasing the relative abundance of Firmicutes. RA significantly boosted the relative abundance of SCFAs by increasing SCFAs-producing bacteria such as Bacteroides, Alloprevotella, Desulfovibrio, etc. In summary, RA could regulate triglyceride metabolism and glycerophospholipid metabolism, restore gut microbiota structure, and increase the relative abundance of SCFAs-producing bacteria to exert its hypolipidemic effects. These findings suggest RA to be a promising therapeutic agent for hyperlipidemia.

Functional metagenomic and metabolomics analysis of gut dysbiosis induced by hyperoxia.

Inhaled oxygen is the first-line therapeutic approach for maintaining tissue oxygenation in critically ill patients, but usually exposes patients to damaging hyperoxia. Hyperoxia adversely increases the oxygen tension in the gut lumen which harbors the trillions of microorganisms playing an important role in host metabolism and immunity. Nevertheless, the effects of hyperoxia on gut microbiome and metabolome remain unclear, and metagenomic and metabolomics analysis were performed in this mouse study. C57BL/6 mice were randomly divided into a control (CON) group exposed to room air with fractional inspired oxygen (FiO2) of 21% and a hyperoxia (OXY) group exposed to FiO2 of 80% for 7 days, respectively. Fecal pellets were collected on day 7 and subjected to metagenomic sequencing. Another experiment with the same design was performed to explore the impact of hyperoxia on gut and serum metabolome. Fecal pellets and blood were collected and high-performance liquid chromatography with mass spectrometric analysis was carried out. At the phylum level, hyperoxia increased the ratio of Firmicutes/Bacteroidetes (p = 0.049). At the species level, hyperoxia reduced the abundance of Muribaculaceae bacterium Isolate-037 (p = 0.007), Isolate-114 (p = 0.010), and Isolate-043 (p = 0.011) etc. Linear discriminant analysis effect size (LEfSe) revealed that Muribaculaceae and Muribaculaceae bacterium Isolate-037, both belonging to Bacteroidetes, were the marker microbes of the CON group, while Firmicutes was the marker microbes of the OXY group. Metagenomic analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active enZYmes (CAZy) revealed that hyperoxia provoked disturbances in carbohydrate and lipid metabolism. Fecal metabolomics analysis showed hyperoxia reduced 11-dehydro Thromboxane B2-d4 biosynthesis (p = 1.10 × 10-11). Hyperoxia blunted fecal linoleic acid metabolism (p = 0.008) and alpha-linolenic acid metabolism (p = 0.014). We showed that 1-docosanoyl-glycer-3-phosphate (p = 1.58 × 10-10) was the most significant differential serum metabolite inhibited by hyperoxia. In addition, hyperoxia suppressed serum hypoxia-inducible factor-1 (HIF-1, p = 0.007) and glucagon signaling pathways (p = 0.007). Hyperoxia leads to gut dysbiosis by eliminating beneficial and oxygen strictly intolerant Muribaculaceae with genomic dysfunction of carbohydrate and lipid metabolism. In addition, hyperoxia suppresses unsaturated fatty acid metabolism in the gut and inhibits the HIF-1 and glucagon signaling pathways in the serum.

LncRNA Tug1 relieves the steatosis of SelenoF-knockout hepatocytes via sponging miR-1934-3p.

Metabolic dysfunction associated with fatty liver disease (MAFLD), always accompanied by disturbance of glucose and lipid metabolism, is becoming the most difficult obstacle in the next decades. In the current research, we uncover that the potent non-coding RNA Tug1, which is related to metabolic enzymes, regulates hepatocytes steatosis induced by sodium palmitate via miR-1934-3p absorbing. The knockdown of lncRNA-Tug1 distinctly rescues the increased expression level of glycolytic enzymes and fatty acid synthetase via releasing more mature miR-1934-3p in hepatocytes. Moreover, miR-1934-3p suppresses Selenoprotein F (SelenoF) through binding with the SelenoF 3'UTR effectors; importantly, we demonstrated that the deletion of SelenoF consistent with the lncRNA-Tug1's effecting on metabolism enzymes. In the current paper, the interaction of Tug1/miR-1934-3p/SelenoF was verified by the dual-luciferase reporter system, and IRS1/AKT pathway possesses the essential role in glucolipid metabolism when SelenoF is deleted. We concluded that lncRNA Tug1 functioned as ceRNA to alleviate steatosis and glycolysis in hepatocytes of C57BL/6 through adsorbing miR-1934-3p to release SelenoF and triggering IRS/AKT pathway. The Tug1/miR-1934-3p/SelenoF constructed the ceRNA interact network Selenoprotein F accelerates glucolipid metabolism via IRS1/AKT pathway SelenoF-/- alleviates steatosis in mice liver.

Adipose Tissue Dynamics: Cellular and Lipid Turnover in Health and Disease.

The alarming increase in obesity and its related metabolic health complications, such as type 2 diabetes, has evolved into a global pandemic. Obesity is mainly characterized by excessive accumulation of adipose tissue, primarily due to an imbalance between energy intake and expenditure. Prolonged positive energy balance leads to the expansion of existing adipocytes (hypertrophy) and/or an increase in preadipocyte and adipocyte number (hyperplasia) to accommodate excess energy intake. However, obesity is not solely defined by increases in adipocyte size and number. The turnover of adipose tissue cells also plays a crucial role in the development and progression of obesity. Cell turnover encompasses the processes of cell proliferation, differentiation, and apoptosis, which collectively regulate the overall cell population within adipose tissue. Lipid turnover represents another critical factor that influences how adipose tissue stores and releases energy. Our understanding of adipose tissue lipid turnover in humans remains limited due to the slow rate of turnover and methodological constraints. Nonetheless, disturbances in lipid metabolism are strongly associated with altered adipose tissue lipid turnover. In obesity, there is a decreased rate of triglyceride removal (lipolysis followed by oxidation), leading to the accumulation of triglycerides over time. This review provides a comprehensive summary of findings from both in vitro and in vivo methods used to study the turnover of adipose cells and lipids in metabolic health and disease. Understanding the mechanisms underlying cellular and lipid turnover in obesity is essential for developing strategies to mitigate the adverse effects of excess adiposity.

Integration of Transcriptomics and Lipidomics Profiling to Reveal the Therapeutic Mechanism Underlying Ramulus mori (Sangzhi) Alkaloids for the Treatment of Liver Lipid Metabolic Disturbance in High-Fat-Diet/Streptozotocin-Induced Diabetic Mice.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder, with a global prevalence of 25%. Currently, there remains no approved therapy. Ramulus mori (Sangzhi) alkaloids (SZ-As), a novel natural medicine, have achieved comprehensive benefits in the treatment of type 2 diabetes; however, few studies have focused on its role in ameliorating hepatic lipid metabolic disturbance. Herein, the therapeutic effect and mechanism of SZ-As on a high-fat diet (HFD) combined with streptozotocin (STZ)-induced NAFLD mice were investigated via incorporating transcriptomics and lipidomics. SZ-As reduced body weight and hepatic lipid levels, restored pathological alternation and converted the blood biochemistry perturbations. SZ-A treatment also remarkedly inhibited lipogenesis and enhanced lipolysis, fatty acid oxidation and thermogenesis. Transcriptomics analysis confirmed that SZ-As mainly altered fatty acid oxidative metabolism and the TNF signaling pathway. SZ-As were further demonstrated to downregulate inflammatory factors and effectively ameliorate hepatic inflammation. Lipidomics analysis also suggested that SZ-As affected differential lipids including triglyceride (TG) and phosphatidylcholine (PC) expression, and the main metabolic pathways included glycerophospholipid, sphingomyelins and choline metabolism. Collectively, combined with transcriptomics and metabolomics data, it is suggested that SZ-As exert their therapeutic effect on NAFLD possibly through regulating lipid metabolism pathways (glycerophospholipid metabolism and choline metabolism) and increasing levels of PC and lysophosphatidylcholine (LPC) metabolites. This study provides the basis for more widespread clinical applications of SZ-As.

Dapagliflozin alleviates renal podocyte pyroptosis via regulation of the HO‑1/NLRP3 axis.

Diabetic nephropathy is one of the most significant complications of diabetes, resulting in increased patient mortality. Dapagliflozin is an inhibitor of sodium‑glucose cotransporter 2 that has an important protective effect on the kidney. Recent studies showed that pyroptosis is involved in the advancement of diabetic nephropathy (DN). However, the potential molecular mechanisms underlying the association between pyroptosis and renal podocyte injury in DN remain unclear. Thus, the present study investigated the anti‑pyroptotic function of dapagliflozin in podocytes and further clarified the potential mechanisms. In this study, a model of lipid metabolism disturbance was established through palmitic acid (PA) induction in a mouse podocyte clone 5 (MPC5) cell line. MPC5 PA‑induced pyroptosis was measured by ELISA, western blotting, quantitative PCR and Hoechst 33342/propidium iodide double‑fluorescence staining. The protective role of HO‑1 was measured using knockdown and overexpression experiments. It was found that dapagliflozin attenuated the expression of pyroptosis‑related proteins, including nucleotide oligomerization domain‑like receptor thermal protein domain associated protein 3, apoptosis‑associated speck‑like protein containing a caspase activation and recruitment domain, caspase‑1, IL‑18 and IL‑1β in the PA group. Meanwhile, the heme oxygenase 1 (HO‑1) expression level decreased within PA, an effect that was reversed by dapagliflozin. Furthermore, the expression of pyroptosis‑related proteins and inflammatory cytokines was reduced following HO‑1 overexpression. Therefore, these results suggested that dapagliflozin ameliorates MPC5 pyroptosis by mediating HO‑1, which has a protective effect on diabetic nephropathy.

An untargeted serum and urine lipidomics research based on UPLC-MS revealed the lipid alterations on adjuvant-induced arthritis rats.

Rheumatoid arthritis (RA) is a systemic autoimmune disease dominated by chronic inflammatory lesions of peripheral synovial joints. Growing evidence suggests that abnormal lipid metabolism levels contribute to the progression of RA. Although several metabolomics studies have shown abnormality in the RA lipidome, the relationship between the overall lipid metabolites and RA has not been systematically evaluated. In this study, an untargeted lipidomics method based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the serum and urine lipidomes of adjuvant-induced arthritis rats to study the characteristics of lipid metabolism changes in the rats and search lipid markers for diagnosing RA. By combining with orthogonal partial least squares discriminant analysis, a total of 52 potential lipid markers were identified, mainly involved in sphingolipid metabolism, glycerophospholipid metabolism, sterol lipid metabolism, glycerolipid metabolism and fatty acid metabolism, which provided crucial insight into lipid metabolism disturbances in RA. Further receiver operating characteristic analysis revealed that the areas under the curve of PC(22:4/16:0), PI(18:1/16:0) and LacCer(d18:1/12:0) from serum and 25-hydroxycholesterol from urine were 0.94, 1.00, 1.00 and 1.00, respectively, indicating the high predictive ability of this method for RA. In this study, our results indicated that a combination of serum and urine analysis can provide a more comprehensive and reliable assessment of RA, and a UPLC-MS-based lipidomics strategy is a powerful tool to search for potential lipid markers associated with RA and explore the pathogenesis of RA.

Association of HDL Subfraction Profile with the Progression of Insulin Resistance.

Type 2 diabetes mellitus (T2DM) is a major global public health problem, as it is associated with increased morbidity, mortality, and healthcare costs. Insulin resistance (IR) is a condition characterized by disturbances in carbohydrate and lipid metabolism that precedes T2DM. The aim of the present study was to investigate the association between HDL and its subfraction profile and the progression of IR, as assessed by the Homeostatic Model Assessment for IR (HOMA-IR) index, and to define cut-off values to identify an increased risk of IR. Individuals with a HOMA-IR greater than 3.63 were considered to have IR. The HDL subfractions were separated using the Lipoprint system, which identifies ten subfractions (HDL-1-10) in three subclasses as large (HDL-L), intermediate (HDL-I) and small (HDL-S). Analyses were performed on samples from 240 individuals without IR and 137 with IR from the Hungarian general and Roma populations. The HDL-1 to -6 subfractions and the HDL-L and -I classes showed a significant negative association with the progression and existence of IR. Among them, HDL-2 (B = -40.37, p = 2.08 × 10-11) and HDL-L (B = -14.85, p = 9.52 × 10-10) showed the strongest correlation. The optimal threshold was found to be 0.264 mmol/L for HDL-L and 0.102 mmol/L and above for HDL-2. Individuals with HDL-L levels below the reference value had a 5.1-fold higher risk of IR (p = 2.2 × 10-7), while those with HDL-2 levels had a 4.2-fold higher risk (p = 3.0 × 10-6). This study demonstrates that the HDL subfraction profile (especially the decrease in HDL-2 and -L) may be a useful marker for the early detection and intervention of atherogenic dyslipidemia in subjects with impaired glucose and insulin metabolism.

PM2.5 exposure aggravates kidney damage by facilitating the lipid metabolism disorder in diabetic mice.

Ambient fine particulate matter ≤ 2.5 µm (PM2.5) air pollution exposure has been identified as a global health threat, the epidemiological evidence suggests that PM2.5 increased the risk of chronic kidney disease (CKD) among the diabetes mellitus (DM) patients. Despite the growing body of research on PM2.5 exposure, there has been limited investigation into its impact on the kidneys and the underlying mechanisms. Past studies have demonstrated that PM2.5 exposure can lead to lipid metabolism disorder, which has been linked to the development and progression of diabetic kidney disease (DKD). In this study, db/db mice were exposed to different dosage PM2.5 for 8 weeks. The effect of PM2.5 exposure was analysis by assessment of renal function, pathological staining, immunohistochemical (IHC), quantitative real-time PCR (qPCR) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) based metabolomic analyses. The increasing of Oil Red staining area and adipose differentiation related protein (ADRP) expression detected by IHC staining indicated more ectopic lipid accumulation in kidney after PM2.5 exposure, and the increasing of SREBP-1 and the declining of ATGL detected by IHC staining and qPCR indicated the disorder of lipid synthesisandlipolysis in DKD mice kidney after PM2.5 exposure. The expressions of high mobility group nucleosome binding protein 1 (HMGN1) and kidney injury molecule 1 (KIM-1) that are associated with kidney damage increased in kidney after PM2.5 exposure. Correlation analysis indicated that there was a relationship between HMGN1-KIM-1 and lipid metabolic markers. In addition, kidneys of mice were analyzed using LC-MS/MS based metabolomic analyses. PM2.5 exposure altered metabolic profiles in the mice kidney, including 50 metabolites. In conclusion the results of this study show that PM2.5 exposure lead to abnormal renal function and further promotes renal injury by disturbance of renal lipid metabolism and alter metabolic profiles.

Association of low HDL-c levels with severe symptoms and poor clinical prognosis in patients with severe fever and thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel bunyavirus, characterized by high fever, thrombocytopenia, and multiple organ damage. Disturbances in lipid metabolism often occur during viral infections, but the changes and clinical significance of lipid profiles in SFTS patients remain unclear. This study aimed to investigate the alterations in lipid profiles and their clinical significance in SFTS patients. A total of 157 SFTS patients and 157 healthy controls were enrolled in this study. Serum lipid levels were collected and analyzed among different groups and prognosis categories. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of lipid levels in distinguishing between severe and mild cases, as well as surviving and non-surviving patients. Pearson correlation analysis was used to examine the associations between lipid levels and clinical laboratory parameters. SFTS patients exhibited significantly lower levels of HDL-c, LDL-c, cholesterol, APoAI, and ApoB compared to healthy controls, while triglyceride levels were significantly higher. Serum HDL-c and ApoAI demonstrated good performance as indicators for distinguishing between survivors and non-survivors (AUC of 0.87 and 0.85, respectively). Multivariate regression analysis indicated that HDL-c independently acts as a protective factor in patients with SFTS. HDL-c levels showed decline in non-survivors but recovered in survivors. Moreover, HDL-c exhibited significant correlations with various clinical laboratory parameters (IL-6, CRP, AST, TT, APTT, PLT, ALB, and CD4). This study identified abnormalities in serum lipid metabolism among SFTS patients. HDL-c and ApoAI levels hold potential as biomarkers for distinguishing survivors from non-survivors. Additionally, HDL-c and ApoAI may serve as therapeutic targets for the management of SFTS patients.

Effects of early exercise on cardiac function and lipid metabolism pathway in heart failure.

We employed an early training exercise program, immediately after recovery from surgery, and before severe cardiac hypertrophy, to study the underlying mechanism involved with the amelioration of cardiac dysfunction in aortic stenosis (AS) rats. As ET induces angiogenesis and oxygen support, we aimed to verify the effect of exercise on myocardial lipid metabolism disturbance. Wistar rats were divided into Sham, trained Sham (ShamT), AS and trained AS (AST). The exercise consisted of 5-week sessions of treadmill running for 16 weeks. Statistical analysis was conducted by anova or Kruskal-Wallis test and Goodman test. A global correlation between variables was also performed using a two-tailed Pearson's correlation test. AST rats displayed a higher functional capacity and a lower cardiac remodelling and dysfunction when compared to AS, as well as the myocardial capillary rarefaction was prevented. Regarding metabolic properties, immunoblotting and enzymatic assay raised beneficial effects of exercise on fatty acid transport and oxidation pathways. The correlation assessment indicated a positive correlation between variables of angiogenesis and FA utilisation, as well as between metabolism and echocardiographic parameters. In conclusion, early exercise improves exercise tolerance and attenuates cardiac structural and functional remodelling. In parallel, exercise attenuated myocardial capillary and lipid metabolism derangement in rats with aortic stenosis-induced heart failure.

Remnant Cholesterol, a Valuable Biomarker for Assessing Arteriosclerosis and Cardiovascular Risk: A Systematic Review.

Arteriosclerosis, as the foundation for the development of cardiovascular diseases, is influenced by disturbances in lipid metabolism. Extensive research has consistently shown a correlation between conventional lipid parameters, arteriosclerosis, and cardiovascular diseases. Guidelines highlight the importance of targeting low-density lipoprotein cholesterol (LDL-C) for primary and secondary prevention of cardiovascular diseases, with reducing LDL-C remaining the primary lipid-lowering strategy. However, even when LDL-C is lowered to optimal levels, there is a residual risk of cardiovascular disease. Recent findings have brought attention to remnant cholesterol (RC) as a significant factor contributing to this residual risk. The close association between RC, arteriosclerosis, and cardiovascular diseases presents exciting opportunities for lifestyle interventions and medical treatments to control and lower RC levels, offering new targets for preventing and managing related cardiovascular conditions. Our systematic review sheds light on the importance of considering RC as a valuable biomarker in assessing arteriosclerosis and its potential impact on cardiovascular health. By understanding the link between remnant cholesterol and arteriosclerosis, researchers and healthcare professionals can develop targeted interventions to mitigate cardiovascular risks, thus improving public health outcomes and reducing the economic burden associated with cardiovascular diseases.

Study of Serum Chemerin Level in Chronic Hepatitis C Virus Patients with and without Nonalcoholic Fatty Liver Disease

Abstract Background Chronic hepatitis C (CHC) has a number of features that suggest that it should be recognized not only as a viral disease but also as a metabolic liver disease that encompasses insulin resistance (IR), liver steatosis, impaired glucose tolerance or type 2 diabetes mellitus (T2DM) and disturbances in lipid metabolism. Objective To evaluate the role of serum Chemerin as a biomarker in patients with chronic hepatitis C virus with and without Non Alcoholic Fatty Liver Disease and its correlation to disease progress and activity and to evaluate its relationship with various laboratory parameters of the disease. Patients and Methods Type of study: A case control study. Study setting: outpatient clinics and inpatient wards at King Fahd hospital, Medina, Saudi Arabia & outpatient clinics at Ain Shams university hospitals, Egypt. Study Period: 6 months. Study Population: The study was conducted on normal populations, chronic HCV patients with NAFLD, and chronic HCV patients without NAFLD. Results In the present study the mean chemerin level was found to be statistically higher in chronic hepatitis C virus patients with NAFLD group compared to chronic hepatitis C virus patients without NAFLD group and was found to be statistically higher in both previous groups than in control group (p value <0.05). There was significant positive correlation between serum chemerin with ALT (p value <0.01), AST (p value<0.01), BMI (P value<0.01), INR (p value<0.01), triglyceride (p value<0.01), FIB4 index (p value <0.01) and NAFLD fibrosis score (p value <0.01). There was significant negative correlation between serum chemerin with serum ALBUMIN (p value <0.01). Conclusion The results obtained in the current study demonstrate that the serum chemerin level increased in parallel with the worsening liver functional reserves in CHC patients and serum chemerin level incrased in patients with CHC associated with NAFLD. It could be concluded that chemerin may be considered as additional tools for assessment of prognosis of CHC and monitoring the virally derived metabolic abnormality.

Lipid and glucose metabolism in senescence.

Senescence is an inevitable biological process. Disturbances in glucose and lipid metabolism are essential features of cellular senescence. Given the important roles of these types of metabolism, we review the evidence for how key metabolic enzymes influence senescence and how senescence-related secretory phenotypes, autophagy, apoptosis, insulin signaling pathways, and environmental factors modulate glucose and lipid homeostasis. We also discuss the metabolic alterations in abnormal senescence diseases and anti-cancer therapies that target senescence through metabolic interventions. Our work offers insights for developing pharmacological strategies to combat senescence and cancer.

Trophic transfer of nanoplastics and di(2-ethylhexyl) phthalate in a freshwater food chain (Chlorella Pyrenoidosa-Daphnia magna-Micropterus salmoides) induced disturbance of lipid metabolism in fish

Nanoplastics and di(2-ethylhexyl) phthalate (DEHP) are ubiquitous emerging contaminants that are transferred among organisms through food chain in the ecosystem. This study evaluated the trophic transfer of polystyrene nanoplastics (PSNPs) and DEHP in a food chain including Chlorella pyrenoidosa, Daphnia magna and Micropterus salmoides (algae-crustacean-fish) and lipid metabolism at a higher trophic level in fish. Our results showed that the PSNPs and DEHP accumulated in C. pyrenoidosa or D. magna were transferred to the M. salmoides, of which the DEHP were not biomagnified, while the PSNPs were trophically amplified by the food chain. It is suggested that more PSNPs might be accumulated by higher level consumers in a longer food chain. Additionally, the trophic transfer of PSNPs and DEHP resulted in antioxidant response and histopathological damage in M. salmoides. Moreover, the lipid biochemical parameters and lipid metabolism related genes (fasn, hsl, cpt1a, atgl, apob, fabp1, lpl, cetp) of M. salmoides were significantly affected, which indicated disturbance of lipid metabolism. This study offers great insight into the transfer of contaminants by trophic transfer and their negative effects on organisms at higher trophic levels, which cause human exposure to MNPs and organic contaminants in the ecosystem.

Intravascular hemolysis triggers NAFLD characterized by a deregulation of lipid metabolism and lipophagy blockade.

Intravascular hemolysis is a common feature of different clinical entities, including sickle cell disease and malaria. Chronic hemolytic disorders are associated with hepatic damage; however, it is unknown whether heme disturbs lipid metabolism and promotes liver steatosis, thereby favoring the progression to nonalcoholic fatty liver disease (NAFLD). Using an experimental model of acute intravascular hemolysis, we report here the presence of liver injury in association with microvesicular lipid droplet deposition. Hemolysis promoted serum hyperlipidemia and altered intrahepatic triglyceride fatty acid composition, with increments in oleic, palmitoleic, and palmitic acids. These findings were related to augmented expression of transporters involved in fatty acid uptake (CD36 and MSR1) and deregulation of LDL transport, as demonstrated by decreased levels of LDL receptor and increased PCSK9 expression. Hemolysis also upregulated hepatic enzymes associated with cholesterol biosynthesis (SREBP2, HMGC1, LCAT, SOAT1) and transcription factors regulating lipid metabolism (SREBP1). Increased LC3II/LC3I ratio and p62/SQSTM1 protein levels were reported in mice with intravascular hemolysis and hepatocytes stimulated with heme, indicating a blockade of lipophagy. In cultured hepatocytes, cell pretreatment with the autophagy inductor rapamycin diminished heme-mediated toxicity and accumulation of lipid droplets. In conclusion, intravascular hemolysis enhances liver damage by exacerbating lipid accumulation and blocking the lipophagy pathway, thereby promoting NAFLD. These new findings have a high translational potential as a novel NAFLD-promoting mechanism in individuals suffering from severe hemolysis episodes. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.