Lipid Metabolism Disorders Research Articles

Exosomes Derived from Diabetic Microenvironment-Preconditioned Mesenchymal Stem Cells Ameliorate Nonalcoholic Fatty Liver Disease and Inhibit Pyroptosis of Hepatocytes

AimPyroptosis, a type of programmed cell death, is a key mechanism underlying non-alcoholic fatty liver disease (NAFLD). Mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) have the potential to ameliorate NAFLD, an effect that is enhanced by curcumin preconditioning. We previously reported that diabetic microenvironment preconditioning enhances the secretion capacity and anti-inflammatory activity of MSCs. Therefore, we hypothesized that MSC-Exos would inhibit hepatocyte pyroptosis and thereby ameliorate NAFLD, and that diabetic microenvironment preconditioning would enhance these effects. MethodsMSCs were preconditioned in a diabetic microenvironment (pMSCs). MSC-Exos and pMSC-Exos collected from MSCs or pMSCs were applied to methionine- and choline-deficient (MCD)-induced NAFLD mice and in vitro models involving induction with lipopolysaccharide or palmitic acid to mimic hepatic steatosis and injury. MCC950 treatment was used as a positive control. We analyzed the characteristics of NAFLD and pyroptosis markers. Protein profiles of MSC-Exos and pMSC-Exos were evaluated by label-free quantitative proteomics. ResultsIn vivo, MSC-Exos partially attenuated inflammation and fibrosis, but not lipid deposition and NAFLD progression in the livers of NAFLD mice. pMSC-Exos significantly improved lipid metabolism, hepatic steatosis, inflammation, and fibrosis but also retarded the progression of NAFLD. Pyroptosis was upregulated in the liver of NAFLD mice. MSC-Exos and pMSC-Exos inhibited pyroptosis, and the effect of the latter was greater than that of the former. In vitro, MSC-Exos and pMSC-Exos ameliorated hepatocyte steatosis, lipid metabolism disorder, and inflammation, and pMSC-Exos exerted a greater inhibitory effect on hepatocyte pyroptosis than MSC-Exos did, which were remitted after inhibition of peroxiredoxin-1 (PRDX-1). ConclusionMSC-Exos ameliorated NAFLD and inhibited hepatocyte pyroptosis by downregulating the NLRP3/Caspase-1/GSDMD pathway, effects enhanced by pMSC-Exos, partly due to PRDX-1 upregulation.

Prevention of iron deficiency conditions in obese children

Background. Due to the progressive increase in childhood obesity, the effect of iron levels in the body on carbohydrate and lipid metabolism disorders and the relationship between these conditions are actively studied. It is proven that obesity in children is often associated with dysregulation of iron metabolism. The correlation between the body mass index and iron deficiency (ID) in children and adolescents was reported. Therefore, implementing preventive measures to correct the iron deficiency state (IDS), including the enrichment of the diet with foods containing easily digestible iron, is relevant and can be considered as one of the principles of an integrated approach to the treatment of obesity in childhood. Aim. To evaluate the effectiveness of dietary supplements "Kidz Tasty iron" for IDS prevention in obese children. Materials and methods. Thirty children aged 7–14 with exogenous constitutional obesity were followed up, 14 (47%) females and 16 (53%) males. All patients received a dietary supplement (DS), "Kidz Tasty iron," 10 mL once daily with meals according to the label for 1 month. The follow-up included data on signs and symptoms, medical history, evaluation of anthropometric data, evaluation of current nutrition status with the software "Optimal Nutrition 5.0", bioimpedance analysis of body composition, questionnaire on the assessment of ID symptoms and quality of life, general hematology and blood chemistry tests, validated for childhood. Results. The diets of obese children in the study had low iron content (33.3% of patients), which justifies the need for additional iron supplementation. While taking the dietary supplement "Kidz Tasty Iron," there was a positive clinical trend: decreased symptoms related to ID and clinical signs of ID, improved overall well-being, and increased quality of life. The improvement of the body composition of the studied children was represented by preservation and an increase (20% of patients) in the active cell mass in the studied children. Laboratory tests of iron metabolism improved in 9 children (30%). Most children reported the good organoleptic properties of the product. Adherence to the DS was 96.7%. Conclusion. The study results show the "Kidz Tasty iron" dietary supplement to be tolerable, safe, and effective, supporting its use in the complex therapy of children and adolescents with obesity, including for IDS prevention.

Developing a photoacoustic probe for in vivo imaging of carboxylesterase in lipid metabolic disorders

Developing a photoacoustic probe for in vivo imaging of carboxylesterase in lipid metabolic disorders

Effects of aquatic Ca2+ and Mg2+ on the antioxidant, immune, osmotic regulation, molting, and metabolic abilities of Scylla paramamosain

Current saline-alkali aquaculture of the saline alkali-tolerant mud crab Scylla paramamosain fails to meet market demand. Given that Ca2+ and Mg2+ are closely related to growth in crustaceans, physiological responses of mud crab to different levels of these ions at varying salinity levels were explored. Long-term aquaculture experiments were conducted by adding CaCl2, MgCl2, and NaCl to the water to control Ca2+, Mg2+ and salinity levels. Three different ratios and concentrations of Ca2+ and Mg2+ were established (Sanmen area, SM group; Cangnan area, CN group; Rui'an area, RA group); in addition, four different salinity groups (3, 8, 10, and 12 ‰) were established under each of the Ca2+–Mg2+ treatment groups At Ca2+:Mg2+ ratios of 300:900 (SM) and 400:1200 mg (CN), S. paramamosain showed stronger osmotic regulation and higher Na+/K+-ATPase and Ca2+/Mg2+-ATPase activity compared with those reared at a Ca2+: Mg2+ ratio of 300:300 (RA). Indicators of hepatopancreas injury also increased in the RA group with time, indicating lipid metabolism disorders and abnormal inflammatory reactions. Immune and antioxidant enzyme activity increased with time in the SM and CN groups, but decreased in the RA group. In addition, malondialdehyde increased with time in the RA group, but remained constant in the SM and CN groups under normal salinity and decreased under low salinity. Thus, cultivation under 300: 900 or 400: 1200 Ca2+: Mg2+ ratios enhanced the immune and antioxidant abilities of mud crab, as well as its ability to alleviate damage caused by low-salt stress. Upregulation of various energy substrates in the CN group under low-salt stress indicated the mobilization of energy reserves to support osmotic regulation. At a salinity of 3 ‰, the CN group also had more pathways upregulated related to energy metabolism, ion transport, and antioxidation, whereas, at 12 ‰, more antioxidant pathways were upregulated. A 120-day aquacultural experiment confirmed that the SM and CN groups showed better growth performance compared with the RA group. Overall, these results confirm that conditions in the SM and CN groups were more suitable for the aquaculture of mud crab, providing a theoretical guidance for increasing mud crab production in saline-alkali fishery.

Multi-omics reveals the beneficial effect of Scytosiphon lomentaria fucoidan on glucose and lipid metabolism disorders via regulation of the gut-liver axis in pregnant mice

Multi-omics reveals the beneficial effect of Scytosiphon lomentaria fucoidan on glucose and lipid metabolism disorders via regulation of the gut-liver axis in pregnant mice

Methyl Donor Micronutrients Orchestrate Lipid Metabolism: The Role of DNA Methylation Modification

DNA methylation, a key epigenetic modification, plays a crucial role in regulating lipid metabolism. Consistent correlations have been observed between aberrant DNA methylation patterns and lipid metabolic disorders. Emerging evidence indicates that methyl donor micronutrients could influence DNA methylation patterns, consequently exerting an influence on lipid metabolism. Specifically, the deficiency or excesses of methyl donor micronutrients (folate, choline, betaine, B vitamins and methionine) have been associated with altered DNA methylation patterns linked to lipid metabolism. These alteration in DNA methylation levels, occurring globally and within promoter regions, could affect gene expression related to lipid metabolism. However, the mechanisms through which methyl donor micronutrients regulate lipid metabolism via the DNA methylation modification and the role of methyl donor micronutrients supplementation on DNA methylation profiles remain unclear. In this review, we summarized the regulatory role of DNA methylation in lipid metabolism, and highlighted recent findings investigating the impact of methyl donor micronutrients on lipid metabolism, as well as DNA methylation-mediated adipogenesis and adipose deposition. Taken together, this review deepened our understanding of how the complex interplay between methyl donor micronutrients, DNA methylation, and lipid metabolism, and provides valuable information for accurately regulating lipid metabolism of livestock and poultry, thereby improving meat quality, and promoting the development of animal husbandry.

The association between N-nitrosamines exposure and lipid metabolism in the high incidence area of esophageal cancer: A case-control analysis

Environmental carcinogens such as N-nitrosamines are high-risk factors for the development of esophageal cancer (EC). However, the association between nitrosamines exposure and lipid metabolism disorders in human EC remained largely obscure. Therefore, we conducted a population-based case-control study established with esophageal inflammation (BCH), esophageal heterotrophic hyperplasia (DYS), patients with primary EC and matched controls in high prevalence area of EC in China. Our prospective work investigated the joint and independent effects of N-nitrosamines co-exposure on the risk of EC development. Lipidomics analysis was employed to screen differential lipid biomarkers in serum, and the mediating effects of key lipid metabolites in the association between nitrosamines exposure and EC were evaluated. After adjustment for confounders, N-nitrosodimethylamine (NDMA, 1.79 (95% CI: 1.35, 2.39)), N-nitrosodi-n-propylamine (NDPA, 1.55 (95%CI: 1.15, 2.09)), N-nitrosodiethylamine (NDEA, 1.82 (95%CI: 1.36, 2.45)), N-nitrosodibutylamine (NDBA, 1.60 (95%CI: 1.20, 2.13)), N-nitrosomethylethylamine (NMEA, 1.81 (95%CI: 1.36, 2.41)) and N-nitrosomorpholine (NMOR, 1.84 (95%CI: 1.38, 2.45)) exposure all elevated the risks of EC development. The Bayesian kernel machine regression (BKMR) with hierarchical variable selection showed significant positive joint associations of urinary NDMA, NDPA, NMOR, NDEA and EC development, when all nitrosamines were at the 55th percentiles or above, compared with the median. Lipidomic screening of serum samples from the stages of BCH, DYS and EC suggested the perturbation in the biosynthesis of unsaturated fatty acid metabolism pathway, of which myristic acid (FFA 14:0), palmitoleic acid (FFA 16:1), docosahexaenoic acid (FFA 22:6) exerted remarkable mediation effects in the association between N-nitrosamines exposure and EC development. These findings provided new sights for screening early lipid biomarkers and intervention targets in human EC.

Early impaired insulin tolerance among Vietnamese diabetes with or without dyslipidemia.

This study aims to evaluate impaired insulin tolerance among Vietnamese diabetes with or without dyslipidemia. Diabetes mellitus (DM) remains the serious global health and social burden that has increased over the past few decades. It progresses silently to vascular injury and disability of injured vascular-perfused tissues/organs. Insulin intolerance and dyslipidemia exacerbate and accelerate the implications of DM. Thus, early detection and more evidence of early insulin intolerance and dyslipidemia is needed for proactive management. This cross-sectional descriptive study recruited 100 healthy control (HC) and 297 DM patients in Military Hospital 103 from 2021 to 2023. Patients with DM were subgrouped into lipid metabolism disorder (LMD, n = 98) and non-LMD (NLMD, n = 99). The biochemists' serum levels were measured automatically and the accuracy of the test result was strictly controlled. Insulin tolerance indices (HOMA2-IR, HOMA2-%S and HOMA2-%B) were compared between HC, DM with or without dyslipidemia as well as correlated with lipid ingredients (total Cholesterol, triglyceride, LDL-C and HDL-C). Among DM patients, HOMA2-IR was significantly high and HOMA2-%S and HOMA2-%B were significantly low. HOMA2-IR was higher and HOMA2-%S and HOMA2-%B were lower in DM with LMD than in DM without LMD. In addition, HOMA2-IR was positively correlated with serum cholesterol, triglyceride and LDL-C concentration, and negatively correlated to HDL-C concentration. In contrast, HOMA2-%S and HOMA2-%B was negatively correlated with serum cholesterol, triglyceride and LDL-C, and positively correlated with HDL-C. Impaired insulin intolerance occurred in early stage of DM, and more serious among DM with LMD, compared to DM with NLMD.

The positive effect of ω-3 polyunsaturated fatty acid supplementation on the cognitive function of children and adolescents with lipid metabolism disorders

The positive effect of ω-3 polyunsaturated fatty acid supplementation on the cognitive function of children and adolescents with lipid metabolism disorders

Alcohol consumption and dyslipidemia in children and adolescents: A review

Consumption of low-alcohol products by young people is due to the erroneous opinion that they are safe for health. However, against the background of taking low-alcohol drinks, addiction quickly forms and complications develop, including lipid metabolism disorders. Studies show that consumption of low-concentration ethanol-containing drinks changes the structure and ratio of serum lipoproteins. Changes in serum lipids provoked by alcohol intake are involved in the pathogenesis of a number of chronic non-infectious diseases, including alcoholic fatty liver disease and atherosclerotic cardiovascular diseases. According to the data of an anonymous online survey, which involved 155 young people aged 17–20 (18±0.76) years, 17.4% of them consume low-concentration alcohol more than once a week, and 5.8% consume both low-alcohol drinks and strong alcohol daily. Comprehensive efforts are needed to prevent the spread of alcohol addiction among children and young people: raising the age at which it is possible to purchase alcoholic beverages, increasing penalties in the area of illegal alcohol trafficking, and working in the area of anti-alcohol propaganda.

Artemisia capillaris Thunb. Water Extract Alleviates Metabolic Dysfunction-associated Steatotic Liver Disease Disease by Inhibiting miR-34a-5p to Activate Sirt1-mediated Hepatic Lipid Metabolism

Artemisia capillaris Thunb. (ACT) is a plant in the Asteraceae family. Its traditional effects are to clear away dampness and heat, promote gallbladder and reduce jaundice. Traditional Chinese medicine believes that MASLD is a damp-heat syndrome. The group's previous study showed that Artemisia capillaris Thunb. Water Extract (ACTE) has an improved effect on MASLD. In order to further understand its mechanism of action, this study established a mouse MASLD model and a HepG2 cell lipid droplet model, combined small RNA sequencing and miRNA transfection experiments, to explore the mechanism of ACTE to improve MASLD by modulating miRNA-targeted mRNA. Non-targeted metabolomics method was used to detect and analyze ACTE. This study screened miR-34a-5p and confirmed its target mRNA-Sirtuin 1 (Sirt1). MASLD induced high expression of miR-34a-5p and low expression of Sirt1, and ACE reversed these changes. When overexpressing miR-34a-5p or knocking down Sirt1, the effect of ACE in reducing PO (palmitic acid and oleic acid complex)-induced lipid accumulation in HepG2 cells was attenuated. ACTE reduces the expression of FASN, SCD1, ACC, and SREBP-1c, promotes the expression of CPT-1 and HSL, thereby reducing lipid accumulation. ACTE activates Sirt1 by inhibiting the expression of miR-34a-5p, thereby reducing liver lipid accumulation and improving HFD-induced MASLD. These findings highlight the potential of ACTE in reducing weight, controlling obesity, and improving lipid metabolism disorders.

Impact of Imperata Cylindrica polysaccharide on liver lipid metabolism disorders caused by hyperuricemia

Impact of Imperata Cylindrica polysaccharide on liver lipid metabolism disorders caused by hyperuricemia

Association of ethanolamine desaturase TMEM189-plasmalogen axis with the stability of atherosclerotic plaque and cardiovascular events after acute coronary syndrome

Abstract Background Patients with acute coronary syndrome (ACS) are still at high risk of recurring major adverse cardiovascular events (MACE). Disorders of lipid metabolism play an important role in the pathogenesis and progression of ACS. However, whether there are lipid components that can play an early warning role on the recurrence of MACE in patients with ACS and its potential mechanism is not yet known. Purpose To explore the changes of lipid profile before recurrent MACE in ACS patients, screen lipid molecules related to recurrent MACE, and explore their effects on pathological changes of atherosclerotic plaque. Methods We selected 44 Chinese ACS patients from the ‘Peking and Rotterdam on Mission to Reduce Coronary Artery Disease’ (PRoMISS) study. Among them, patients with recurrent MACE within 1 year after first onset of ACS were defined as MACE group, and the control group was recruited through 1:1 matching. The lipid profile of patients was analyzed by liquid chromatography-mass spectrometry. The effects of the screened potential lipid biomarkers and their synthesis enzymes were evaluated by real-time PCR, Western blot, IHC staining and ELISA. The enzyme knockout mice and ApoE knockout mice were hybridized and bred to obtain double gene knockout mice to determine whether the enzyme deficiency affects atherosclerotic plaque. Results Lipomic analysis showed that in the MACE group, plasmalogens and their 12 subtypes continued to decrease three months before the MACE recurrence. The most critical ethanolamine desaturase in the synthesis pathway of plasmalogen, transmembrane protein 189 (TMEM189) was also significantly lower in the MACE group than in the control group, and the level of TMEM189 was positively correlated with plasmalogen. Analysis of single-cell RNA sequencing results in human carotid artery plaques shows that TMEM189 is enriched in endothelial cells and smooth muscle cells (VSMC). In VSMC, treatment with oxLDL reduced TMEM189 expression. Overexpression of TMEM189 significantly improved oxLDL induced reduction in collagen synthesis, expression of alpha-smooth muscle actin (alpha-SMA) and smooth muscle protein 22 (SM22). Overexpression of TMEM189 in VSMC, significantly reduced the content of plasmalogens in the cells. After 12 weeks of feeding with high-fat and high-cholesterol diet, it was found that the content of smooth muscle cells and vulnerability index in the aortic plaque in TMEM189 -/-ApoE -/- mice were significantly decreased than in ApoE -/- mice. Conclusions Before the recurrence of MACE in ACS patients, the synthesis pathway of plasmalogen was gradually damaged, and the reduction of plasmalogen was a potential marker for predicting the recurrence of MACE in ACS patients. The deficiency of TMEM189 - plasmalogen axis aggravates atherosclerosis, it can regulate the phenotype transformation of smooth muscle cells, inhibit their collagen synthesis, and thus affect plaque stability.

Retinal G-protein-coupled receptor deletion exacerbates AMD-like changes via the PINK1-parkin pathway under oxidative stress.

The intake of high dietary fat has been correlated with the progression of age-related macular degeneration (AMD), affecting the function of the retinal pigment epithelium through oxidative stress. A high-fat diet (HFD) can lead to lipid metabolism disorders, excessive production of circulating free fatty acids, and systemic inflammation by aggravating the degree of oxidative stress. Deletion of the retinal G-protein-coupled receptor (RGR-d) has been identified in drusen. In this study, we investigated how the RGR-d exacerbates AMD-like changes under oxidative stress, both invivo and invitro. Fundus atrophy became evident, at 12 months old, particularly in the RGR-d + HFD group, and fluorescence angiography revealed narrower retinal vessels and a reduced perfusion area in the peripheral retina. Although rod electroretinography revealed decreasing trends in the a- and b-wave amplitudes in the RGR-d + HFD group at 12 months, the changes were not statistically significant. Mice in the RGR-d + HFD group showed a significantly thinner and more fragile retinal morphology than those in the WT + HFD group, with disordered and discontinuous pigment distribution in the RGR-d + HFD mice. Transmission electron microscopy revealed a thickened Bruch's membrane along the choriocapillaris endothelial cell wall in the RGR-d + HFD mice, and the outer nuclear layer structure appeared disorganized, with reduced nuclear density. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated significantly lower levels of 25(OH)-vitamin D3 metabolites in the RGR-d + HFD group. Under oxidative stress, RGR-d localized to the mitochondria and reduced the levels of the PINK1-parkin pathway. RGR-d mice fed an HFD were used as a new animal model of dry AMD. Under high-fat-induced oxidative stress, RGR-d accumulated in the mitochondria, disrupting normal mitophagy and causing cellular damage, thus exacerbating AMD-like changes both invivo and invitro.

VEGFB ameliorates insulin resistance in NAFLD via the PI3K/AKT signal pathway

BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most universal liver diseases with complicated pathogenesis throughout the world. Insulin resistance is a leading risk factor that contributes to the development of NAFLD. Vascular endothelial growth factor B (VEGFB) was described by researchers as contributing to regulating lipid metabolic disorders. Here, we investigated VEGFB as a main target to regulate insulin resistance and metabolic syndrome.MethodsIn this study, bioinformatics, transcriptomics, morphological experiments, and molecular biology were used to explore the role of VEGFB in regulating insulin resistance in NAFLD and its molecular mechanism based on human samples, animal models, and cell models. RNA-seq was performed to analyze the signal pathways associated with VEGFB and NAFLD; Palmitic acid and High-fat diet were used to induce insulin-resistant HepG2 cells model and NAFLD animal model. Intracellular glucolipid contents, glucose uptake, hepatic and serum glucose and lipid levels were examined by Microassay and Elisa. Hematoxylin-eosin staining, Oil Red O staining, and Periodic acid-schiff staining were used to analyze the hepatic steatosis, lipid droplet, and glycogen content in the liver. Western blot and quantitative real-time fluorescent PCR were used to verify the expression levels of the VEGFB and insulin resistance-related signals PI3K/AKT pathway.ResultsWe observed that VEGFB is genetically associated with NAFLD and the PI3K/AKT signal pathway. After VEGFB knockout, glucolipids levels were increased, and glucose uptake ability was decreased in insulin-resistant HepG2 cells. Meanwhile, body weight, blood glucose, blood lipids, and hepatic glucose of NAFLD mice were increased, and hepatic glycogen, glucose tolerance, and insulin sensitivity were decreased. Moreover, VEGFB overexpression reduced glucolipids and insulin resistance levels in HepG2 cells. Specifically, VEGFB/VEGFR1 activates the PI3K/AKT signals by activating p-IRS1Ser307 expression, inhibiting p-FOXO1pS256 and p-GSK3Ser9 expressions to reduce gluconeogenesis and glycogen synthesis in the liver. Moreover, VEGFB could also enhance the expression level of GLUT2 to accelerate glucose transport and reduce blood glucose levels, maintaining glucose homeostasis.ConclusionsOur studies suggest that VEGFB could present a novel strategy for treating NAFLD as a positive factor.Graphical

Circadian Regulation of Lipid Metabolism during Pregnancy.

A cluster of metabolic changes occur to provide energy for fetal growth and development during pregnancy. There is a burgeoning body of research highlighting the pivotal role of circadian rhythms in the pathogenesis of metabolic disorders and lipid homeostasis in mammals. Perturbations of the circadian system and lipid metabolism during gestation might be responsible for a variety of adverse reproductive outcomes comprising miscarriage, gestational diabetes mellitus, and preeclampsia. Growing studies have confirmed that resynchronizing circadian rhythms might alleviate metabolic disturbance. However, there is no clear evidence regarding the specific mechanisms by which the diurnal rhythm regulates lipid metabolism during pregnancy. In this review, we summarize previous knowledge on the strong interaction among the circadian clock, lipid metabolism, and pregnancy. Analyzing the circadian clock genes will improve our understanding of how circadian rhythms are implicated in complex lipid metabolic disorders during pregnancy. Exploring the potential of resynchronizing these circadian rhythms to disrupt abnormal lipid metabolism could also result in a breakthrough in reducing adverse pregnancy outcomes.

Ferulic Acid Alleviates Lipid and Bile Acid Metabolism Disorders by Targeting FASN and CYP7A1 in Iron Overload-Treated Mice

Iron overload is a common complication in various chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD). Lipid and bile acid metabolism disorders are regarded as crucial hallmarks of NAFLD. However, effects of iron accumulation on lipid and bile acid metabolism are not well understood. Ferulic acid (FA) can chelate iron and regulate lipid and bile acid metabolism, but its potential to alleviate lipid and bile acid metabolism disorders caused by iron overload remains unclear. Here, in vitro experiments, iron overload induced oxidative stress, apoptosis, genomic instability, and lipid deposition in AML12 cells. FA reduced lipid and bile acid synthesis while increasing fatty acid β-oxidation and bile acid export, as indicated by increased mRNA expression of PPARα, Acox1, Adipoq, Bsep, and Shp, and decreased mRNA expression of Fasn, Acc, and Cyp7a1. In vivo experiments, FA mitigated liver injury in mice caused by iron overload, as indicated by reduced AST and ALT activities, and decreased iron levels in both serum and liver. RNA-seq results showed that differentially expressed genes were enriched in biological processes related to lipid metabolism, lipid biosynthesis, lipid storage, and transport. Furthermore, FA decreased cholesterol and bile acid contents, downregulated lipogenesis protein FASN, and bile acid synthesis protein CYP7A1. In conclusion, FA can protect the liver from lipid and bile acid metabolism disorders caused by iron overload by targeting FASN and CYP7A1. Consequently, FA, as a dietary supplement, can potentially prevent and treat chronic liver diseases related to iron overload by regulating lipid and bile acid metabolism.

Alkaline Mineral Complex Water Attenuates Transportation-Induced Hepatic Lipid Metabolism Dysregulation by AMPKα-SREBP-1c/PPARα Pathways.

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.

Molecular mechanism of high-altitude hypoxia-induced lipid metabolism disorder in mouse spleen tissue

To investigate the molecular mechanism of lipid metabolism disorder in mouse spleen tissues due to high-altitude hypoxia. Ten C57BL/6 male mice were randomly divided into normoxia group (maintained at an altitude of 400 m) and high-altitude hypoxia group (maintained at 4200 m) for 30 days (n=5). Lipidomics and metabolomics analyses of the spleen tissue of the mice were conducted using liquid chromatography-mass spectrometry (LC-MS) to identify the differential metabolites, which were further analyzed by KEGG enrichment and pathway analyses, and the differential genes were screened through transcriptome sequencing. Bioinformatics analysis was conducted to identify the upstream target genes of the differential metabolites in specific metabolic pathways. RT-qPCR and Western blotting were used to detect mRNA expressions of 11β-hydroxysteroid dehydrogenase 1 (HSD11B1), steroid 5α reductase 1 (SRD5A1), prostaglandin-endoperoxide synthase 1 (PTGS1), hematopoietic prostaglandin D synthetase (HPGDS), xanthine dehydrogenase (XDH), purine nucleoside phosphorylase (PNP), hypoxanthine guanine-phosphoribosyltransferase (HPRT) and extracellular 5'-nucleotidase (NT5E) and protein expressions of HSD11B1, SRD5A1, XDH, PNP and HPRT in the mouse spleens. We identified a total of 41 differential lipid metabolites in the mouse spleens, and these metabolites and the differential genes were enriched in steroid hormone biosynthesis, arachidonic acid metabolism, and purine metabolism pathways. Compared to the mice kept in normoxic conditions, the mice exposed to high-altitude hypoxia showed significantly upregulated expressions of adrenosterone, androsterone, prostaglandin D2, prostaglandin J2, xanthine, xanthosine, and uric acid in the spleen with also changes in the expression levels of HSD11B1, SRD5A1, PTGS1, HPGDS, XDH, PNP, HPRT, and NT5E. High-altitude hypoxia can result in lipid metabolism disorder in mouse spleen tissue by affecting steroid hormone biosynthesis, arachidonic acid metabolism, and purine metabolism pathways.

Lipid metabolism and hearing loss: association of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) with adolescent hearing health

BackgroundThe ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is a novel lipid measure for assessing the risk of cardiovascular disease. Lipid metabolism disorders are reportedly associated with hearing impairment. This study aimed to investigate the potential association between NHHR and hearing.MethodsThe data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) cycles of 2005–2010 and 2017–2018, including 4,296 participants aged 6–19 years. The NHHR was calculated from lipid profiles, and hearing was assessed using pure-tone audiometry. Weighted multivariate logistic regression analyses were used to investigate the association between the NHHR and hearing loss. Subgroup and sensitivity analyses were performed to verify the robustness of the results.ResultsUnivariate analysis revealed significant associations between the NHHR and hearing threshold at all categorized frequency (low, speech, or high-frequency) (P < 0.001). Three models were used: an unadjusted model, a model adjusted for age, sex, and race, and a model further adjusted for PIR, BMI, and diabetes. Multiple regression analysis confirmed these associations consistently across all models. When considered as a continuous variable, NHHR had a significant association with enhanced hearing thresholds at all categorized frequencies: low-frequency (β:0.56, 95% CI: 0.36–0.75), speech-frequency (β:0.55, 95% CI: 0.36–0.7), and high-frequency (β:0.55, 95% CI: 0.36–0.74). The adjusted models showed persistent positive correlations after controlling for covariates. The NHHR was consistently positively associated with hearing loss. The NHHR and auditory thresholds showed a general dose-response association across all frequencies.ConclusionsNHHR is a promising biomarker for predicting adolescent hearing threshold shifts and hearing loss. The study highlights the importance of early lipid monitoring and management as strategies to prevent or reduce hearing impairment.