Lipid Metabolism Disorders Research Articles

Deciphering the impact of heavy metal mixed exposure on lipid metabolism using three statistical models.

Lipid metabolism disorders pose a significant threat to human health. However, the relationship between heavy metal mixed exposure and lipid metabolism remains poorly understood. This study recruited 1717 residents living near a chromium factory in northeast China. The concentrations of blood Cr, Mn, Cd, Pb, V, and serum CHOL, TG, LDL and HDL levels were measured. Generalized linear model (GLM), quantile g-computation (Qg-comp), and Bayesian kernel machine regression (BKMR) were simultaneously employed to investigate the associations between heavy metal mixed exposure and lipid markers levels. GLM analysis revealed significant associations between blood Cr concentration and HDL (β = -0.07; 95%CI: -0.09, -0.05), LDL (β = -0.06; 95%CI: -0.11, -0.02), and CHOL (β = 0.07; 95%CI: 0.01, 0.12) levels. V concentration was positively associated with HDL (β = 0.12; 95%CI: 0.06, 0.18) and LDL (β = 0.17; 95%CI: 0.04, 0.30) levels. Qg-comp analysis indicated a negative association between heavy metal mixed exposure and HDL (β = -0.040; 95%CI: -0.073, -0.006) level. BKMR model further confirmed the negative relationship between heavy metal mixed exposure and HDL, with the interaction between blood Cr (> 1.05μg/L) and blood V (> 5.16μg/L) contributing to decreased HDL levels. Our findings suggested that heavy metal mixed exposure had impacts on HDL and CHOL levels, and the Cr and V may mutually play a predominant role in the observed abnormal HDL levels.

Serpina3c Deficiency Promotes Obesity-related Hypertriglyceridemia and Inflammation through Activation of the Hif1α-glycolysis Axis in Adipose Tissue.

Adipose tissue dysfunction leads to abnormal lipid metabolism and high inflammation levels. This research aims to explore the role of Serpina3c, which is highly expressed in adipocytes, in obesity-related hypertriglyceridemia and metaflammation. Serpina3c global knockout (KO) mice, adipocyte-specific Serpina3c overexpressing mice, Serpina3c knockdown (KD) mice, and hypoxia-inducible factor 1 alpha(Hif1α) KD mice were fed a high-fat diet (HFD) for 16 weeks to generate obesity-related hypertriglyceridemia mice models. In the present study, Serpina3c KO mice and adipocyte-specific Serpina3c KD mice exhibited more severe obesity-related hypertriglyceridemia and metaflammation under HFD conditions. Serpina3c KO epididymal white adipose tissue (eWAT) primary stromal vascular fraction (SVF)-derived adipocytes exhibited higher lipid (triglyceride and non-esterified fatty acid) levels and higher fatty acid synthase expression after palmitic acid stimulation. Adipocyte-specific Serpina3c overexpression in KO mice prevented the KO group phenotype. The RNA-seq and in vitro validation revealed that Hif1α and the glycolysis pathways were upregulated in Serpina3c KD adipocytes, which were all validated by in vitro and in vivo reverse experiments. Co-immunoprecipitation (co-IP) provided evidence that Serpina3c bound nuclear factor erythroid 2-related factor 2 (Nrf2) to regulate Hif1α. Nrf2 KD reduced Hif1α and Fasn expression, decreased lipid content, and reduced the extracellular acidification rate in Serpina3c KO adipocytes. Metabolomics revealed that lactic acid (LD) levels in eWAT were responsible for adipose-associated macrophage inflammation. In summary,Serpina3c inhibits the Hif1α-glycolysis pathway and reduces de novo lipogenesis and LD secretion in adipocytes by binding to Nrf2, thereby improving HFD-induced lipid metabolism disorders and alleviating adipose tissue macrophage inflammation.

Health care concerns in women at midlife: differences by race, ethnicity, and neighborhood socioeconomic status.

The aims of the study were to identify conditions diagnosed in at least 10% of midlife women living in the US upper midwest and to assess prevalence by age, race, ethnicity, and sociodemographic status. The Rochester Epidemiology Project was used to conduct a cross-sectional prevalence study of 86,946 women between 40 and 59 years residing in a 27-county region of the United States on January 1, 2020. Diagnostic billing codes were extracted and grouped into broader condition categories using the Clinical Classification System Refined. The prevalence of 424 conditions was calculated by age, race, ethnicity, and area deprivation index quartiles. Logistic regression was used to examine associations between participant characteristics and conditions that affected 10% or more of the study population. Twenty-eight conditions affected ≥10% of women, and eight conditions increased by ≥45% between the ages of 40 and 59 (disorders of lipid metabolism, hypertension, sleep/wake disorders, thyroid disorders, esophageal disorders, osteoarthritis, tendon and synovial disorders, and menopausal disorders; all test for trend P < 0.01). Black women had a significantly higher prevalence of hypertension and esophageal disorders at all ages (adjusted P values <0.05). Women living in more deprived areas had a significantly higher prevalence of hyperlipidemia, hypertension, sleep/wake disorders, and esophageal disorders (adjusted P values <0.05). Women living in less deprived areas had a significantly higher prevalence of thyroid disorders at age 40 to 44 and menopausal disorders at ages 50 to 59 (adjusted P values <0.05). These data suggest that additional attention should focus on Black women and women with a lower socioeconomic status to ensure that common midlife conditions are diagnosed and treated.

Features of mental state and reproductive function in dynamics inmentally ill women with infertility

Women suffering from a mental disorder are faced with the problem of pregnancy and the realisation of their reproductive rights throughout their lives. The presence of a mental disorder largely determines the onset, course and outcome of pregnancy. A deterioration in mental health is often accompanied by an impairment of menstrual and reproductive function, and an improvement contributes to their recovery.Objective: to analyse individual indicators of reproductive function in women with various mental disorders and infertility in dynamics according to the follow-up data.Material and methods. The study included 120 women with various mental disorders and infertility, who were observed for 2 years by a psychiatrist and a gynaecologist on the background of treatment of the existing disorders.Results. In 70% of cases, mentally ill women have primary infertility, with idiopathic infertility predominating (63.3%), especially in the context of secondary infertility (77.8%; p&lt;0.05). Treatment of infertility by gynaecologists and mental disorders by psychiatrists leads to the normalization of the menstrual cycle and the onset of pregnancy. Pregnancy is usually accompanied by obstetric and somatic complications (fetal growth retardation and miscarriage, placental disorders, hypertension, oedema, lipid metabolism disorders, gestational diabetes mellitus). Reproductive function is impaired mostly in patients with schizophrenia and affective disorders, they account for 80.8% of observed infertility. Fertility is lowest in patients with paranoid schizophrenia: pregnancy occurred in 12.9% of patients, none of them gave birth. In schizoaffective disorder, 43.75% of women became pregnant, but only 20% gave birth. In bipolar affective disorder (BAD) type I, pregnancy occurred in 87.5% of patients (of which 57.1% resulted in a childbirth), in bipolar disorder type II – in 43.75% (of which 42.8% resulted in a childbirth), and in recurrent depressive disorder – in 60% (of which 50% resulted in a childbirth). In these disorders, the duration of infertility correlates with the duration of the disease (p&lt;0.05). In neurotic disorders, fertility suffers to a lesser extent: pregnancy with recovery or significant improvement of the mental condition occurred in 75–100% of cases, but only 66.7% of cases resulted in a child birth. Childbirth was mainly performed by caesarean section.Conclusion. Reproductive function in mentally ill women depends largely on the type of mental disorder, the characteristics of its course, the efficacy of psychopharmacotherapy, the quality of remission and the degree of social and family adaptation, which must be taken into account in the diagnosis and treatment of infertility.

THE ROLE OF ASPROSIN IN LIPID METABOLISM IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND CHRONIC PANCREATITIS

Background. Type 2 Diabetes Mellitus (T2DM) is a highly prevalent metabolic disease that significantly affects patients' quality of life and increases mortality due to complications. Understanding the relationships between T2DM and chronic pancreatitis (CP) is very important, as both conditions significantly impact metabolic processes in the body, particularly lipid metabolism. Asprosin, a recently discovered adipokine, plays a key role in regulating glucose homeostasis and appetite. Its elevated levels are associated with obesity, insulin resistance, and T2DM, making it a potential biomarker for diagnosing and monitoring metabolic disorders. Objective. The objective of this study was to investigate the relationships between asprosin levels and lipid metabolism indicators in patients with T2DM and CP. Materials and Methods. The study included 100 patients treated at the Kharkiv Regional Clinical Hospital from 2020 to 2022, divided into two groups: the first group included 70 patients with T2DM and CP, and the second group consisted of 30 patients with T2DM. The control group consisted of 20 relatively healthy men and women of appropriate age. Asprosin levels were determined by indirect non-competitive heterogeneous enzyme immunoassay. Lipid profile indicators were determined by standard biochemical methods. Correlations were assessed using Pearson's linear correlation coefficient. Results. In the group of patients with T2DM and CP, the level of total cholesterol (TC) was 5.01 ± 0.78 mmol/L, triglycerides (TG) – 2.29±0.84 mmol/L, high-density lipoprotein cholesterol (HDL-C) – 1.19±0.19 mmol/L, low-density lipoprotein cholesterol (LDL-C) – 3.32±1.1 mmol/L, and very low-density lipoprotein cholesterol (VLDL-C) – 0.92±0.47 mmol/L. In the T2DM group, the levels of TC, TG, HDL-C, LDL-C, and VLDL-C were 5.35±1.15, 1.91±0.64, 1.03±0.14, 3.5±0.8, and 0.96±0.51 mmol/L, respectively. In the control group, these indicators were 4.25±1.08, 1.01±0.25, 1.31±0.22, 2.35±0.55, and 0.65±0.21 mmol/L, respectively. The levels of all studied lipid metabolism indicators exhibited statistically significant differences between the control group and both the first and second groups. The highest asprosin level (10.06±3.56 ng/mL) was noted in the group with comorbid type 2 diabetes mellitus and chronic pancreatitis. In the patients with isolated type 2 diabetes mellitus significant moderate correlations between asprosin and total cholesterol, and LDL-C (direct) and HDL-C (reverse) levels were established. In the group of patients with type 2 diabetes mellitus and chronic pancreatitis, significant moderate direct correlations between asprosin and total cholesterol, and LDL-C levels were also established. Conclusions. Asprosin is a new adipokine associated with lipid metabolism disorders, that making it a potential target for therapeutic intervention in type 2 diabetes mellitus and its complications. Further research is needed to better understand the role of asprosin in the pathogenesis of these diseases and to develop new approaches to their treatment.

Polyethylene glycol loxenatide modulates lipid metabolism and insulin resistance through lncRNA steroid receptor RNA activator/cellular nucleic acid binding protein/Rho-associated coiled-coil kinase 2 axis in type 2 diabetes mellitus.

Polyethylene glycol loxenatide (PEG-Loxe) is applied in treating type 2 diabetes mellitus. Nevertheless, the effect and mechanism of PEG-Loxe on lipid metabolism disorder and insulin resistance in type 2 diabetes mellitus are not fully understood. Type 2 diabetes mellitus rats developed by high-fat diet/streptozotocin injection were treated with PEG-Loxe (0.3 or 1 mg/kg). Insulin resistance was evaluated by fasting blood glucose (FBG), oral glucose tolerance test, fasting insulin, homeostasis model of assessment for insulin resistance and for insulin sensitivity. Immunohistochemistry, hematoxylin and eosin staining, and biochemistry measurements were performed to assess lipid metabolism. Inflammatory response and oxidative stress were assessed by inflammatory cytokines and reactive oxygen species. Genes' expressions were tested using RT-qPCR, western blot, and in situ hybridization. Relationships of molecules were validated by pull-down assay and RNA immunoprecipitation. mRNA stability was examined by actinomycin D assay. High-PEG-Loxe decreased FBG and ameliorated glucose tolerance, hyperinsulinemia, and insulin resistance. Low-PEG-Loxe partly while high-PEG-Loxe apparently relieved hepatocyte injury, reduced lipase I, triglyceride, total cholesterol and leptin, and increased adiponectin in type 2 diabetes mellitus rats. PEG-Loxe mitigated inflammatory response and oxidative stress. High-PEG-Loxe reduced RhoA and Rho-associated coiled-coil kinase 2 (ROCK2) in liver tissues of type 2 diabetes mellitus rats, while both doses of PEG-Loxe decreased steroid receptor RNA activator (SRA). SRA overexpression reversed the protective functions of high-PEG-Loxe. SRA cooperated with cellular nucleic acid binding protein (CNBP) to enhance ROCK2 mRNA stability. High-PEG-Loxe relieves insulin resistance and lipid metabolism disorder in type 2 diabetes mellitus through SRA/CNBP/ROCK2 axis. This research provides a molecular mechanism of PEG-Loxe for treating type 2 diabetes mellitus.

Transnational economic development: Pakistani and Indian diaspora in focus

IntroductionType 2 diabetes mellitus (T2DM) often leads to elevated blood glucose levels and lipid metabolism disorder, which is generally accompanied by dysbiosis of gut microbiota and metabolic dysfunction.MethodIn this study, a mouse model of T2DM was established by feeding a high-fat/sucrose diet combined with injecting a low dose of streptozotocin. The aim of this study was to analyze the regulatory effect of Suaeda salsa extract (SSE) on T2DM and its effect on the intestinal flora of mice.ResultsThe results showed that SSE could significantly improve the body weight, fasting blood glucose (FBG), area under the curve (AUC) of the oral glucose tolerance test (OGTT), glycosylated serum protein (GSP) and islet function index. Moreover, 4-week body weight, FBG, AUC of OGTT, GSP, as well as intestinal acetic and butyric acid were significantly better in the SSE-L than in the MET group (p &amp;lt; 0.05). In addition, it was also found that the potential hypoglycemic mechanism of SSE was related to the expression of Akt serine/threonine kinase (AKT-1) and glucose transporter-2 (GLUT-2) genes. Compared with the model group, SSE intervention significantly increased the abundance of probiotics, such as Soleaferrea, Alloprevotella, Lactobacillus and Faecalibaculum, while decreasing the relative abundance of harmful bacteria, such as Phocaeicola and Bilophila. Analysis of the correlation among intestinal microbiota, short chain fatty acids (SCFAs) and the hypoglycemic index showed that Dwaynesavagella was significantly correlated with acetic, propionic and butyric acid, as well as all the diabetes-related indexes analyzed in this study.DiscussionThus, this taxon can potentially be used as a microbiological marker of type 2 diabetes. Taken together, these findings demonstrate that SSE can alleviate T2DM and its complications by improving glycemia-related indicators and modulating the structure of intestinal flora.

Effect of Dendrobium nobile powder combined with conventional therapy on mild to moderate fatty liver.

Nonalcoholic fatty liver disease (NAFLD) encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol. Recently, traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver, among which Dendrobium nobile Lindl. powder has been affirmed by many doctors and patients to be effective. However, there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD. To survey the effect of combining Dendrobium nobile Lindl. powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD. Eighty patients with mild to moderate NAFLD participated in this retrospective study, classified into two groups: The observation group (n = 40) and the control group (n = 40). In November 2020 and November 2022, the study was conducted at People's Hospital of Chongqing Liang Jiang New Area. The control group received standard treatment, while the observation group received Dendrobium nobile Lindl. powder based on the control group. The study compared differences in traditional Chinese medicine clinical syndrome scores, liver fibrosis treatment, liver function indicators, lipid levels, and serum inflammatory factor levels before and after treatment, and we calculated the incidence of adverse reactions for both groups. The total effective rate was 97.50% in the observation group and 72.5% in the control group. After 8 weeks of treatment, the main and secondary symptom scores remarkably decreased, especially in the observation group (P < 0.05), and there was a significant reduction in the serum levels of hyaluronic acid (HA), laminin (LN), human rocollagen III (PC III), and collagen type IV (CIV). The levels of HA, LN, PC III, and CIV were significantly lower in the observation group (P < 0.05). After 8 weeks, both groups indicated remarkable improvements in liver function and blood lipid levels, with the observation group having even lower levels (P < 0.05). Serum levels of interleukin-1β, tumor necrosis factor-α, and interleukin-8 also dropped significantly. The observation group had a lower rate of adverse reactions (5.00%) compared to the control group (22.50%). Adding Dendrobium nobile Lindl. powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease. It also enhances hepatic function and lipid profile, ameliorates liver fibrosis indices, and lowers the risk of side effects. Consequently, this therapeutic protocol shows promise for clinical implementation and dissemination.

Expression and functional analysis of adipokinetic hormone reveal its different roles in larval development and female fecundity in Panonychus citri (McGregor) (Acari: Tetranychidae).

Adipokinetic hormone (AKH), a crucial neuropeptide, participates in the important physiological processes by specially binding to its receptor to activate the AKH signalling pathway. AKH regulates energy metabolism. However, it remains unknown whether AKH affects larval development and adult reproduction by influencing energy metabolism. In the present study, the AKH was identified from Panonychus citri and contained the conserved functional domain 'Q-[LIV]-[NT]-F-[ST]-X (2)-W' that characterises the AKH family. The relative expression levels of PcAKH revealed different patterns of AKH expression at different developmental stages of P. citri. Feeding of double-standard RNA against PcAKH induced decreased fecundity and reduced survival, which was accompanied by the down-regulation of vitellogenin gene expression. In addition, after silencing the PcAKH, lipid metabolism and carbohydrate homeostasis were disrupted, manifested by increased body width and weight, and fasting phenomenon. Further investigation found that compared with the control, physiological changes in trehalose and triglyceride contents were accompanied by variations in the mRNA expression levels of genes related to lipid metabolism and carbohydrate metabolism. The disorder of lipid and carbohydrate metabolism may affect adult female reproduction, which may lead to insufficient vitellogenin deposition. Moreover, the silencing of PcAKH seriously affected the growth and development of larvae, which was manifested as delayed development period and difficulty in moulting. Conclusively, all these results in current study demonstrated that double-stranded RNA silencing system targeting PcAKH effectively inhibited larval development and female fecundity by disturbing lipid and carbohydrate metabolism, and PcAKH is a specific RNAi target for control of P. citri in the design and development of biopesticide in sustainable agriculture.

Evaluation of Hypoglycemic Polyphenolic Compounds in Blueberry Extract: Functional Effects and Mechanisms

Blueberries are rich in polyphenols, which exhibit significant anti-diabetic activity. In this study, polyphenolic compounds with potential hypoglycemic activity were identified from blueberry polyphenol extract (BPE). This research focused on assessing the hypoglycemic effects of BPE and its polyphenolic compounds (dihydroquercetin and gallic acid) on diabetic mice induced by streptozotocin (STZ) and high-fat diet (HFD), as well as the related fundamental mechanisms. The findings revealed that BPE treatment effectively reduced levels of fasting blood glucose (FBG) by decreasing hepatic oxidative stress, regulating lipid metabolism disorders and improving insulin resistance. Investigations into the insulin signaling pathway revealed that BPE can modulate the expression of Egfr, Insr, Irs-1, Pi3k and Akt, thereby influencing glucose metabolism. This study provides a research foundation for considering blueberry polyphenols as a nutritional dietary supplement for the prevention and intervention of diabetes.

Fabrication and Characterization of Gelatin-Finger Citron Polysaccharide Nanoparticles for Enhanced Solubility and Bioavailability of Luteolin in Treating Acute Alcoholic Liver Disease.

Luteolin (Lut) is a natural flavonoid that has been widely used in the treatment of liver and glycolipid metabolic diseases. However, poor water solubility and bioavailability limit its efficacy and application. To overcome these challenges, a protein-polysaccharide composite nanoparticle (L-GF NPs) for Lut delivery was prepared by a self-assembly method based on amphiphilic gelatin and active finger citron polysaccharide (FCP). The L-GF NPs were approximately spherical in shape and were formed by hydrogen bonding, electrostatic interaction, and hydrophobic interaction. Lut was encapsulated in the nanoparticles in an amorphous state, and the encapsulating efficiency was 79.49%. The efficacy of L-GF NPs was evaluated by intragastric administration of an alcoholic liver disease (ALD) mouse model. L-GF NPs have been demonstrated to significantly ameliorate the symptoms of ALD mice, which are mainly achieved by reducing lipid accumulation and oxidative stress and inhibiting the NF-κB pathway. In conclusion, the aqueous solubility and bioavailability of Lut were markedly enhanced by FCP encapsulation. Meanwhile, the combined effect of Lut and FCP significantly ameliorated ALD and attenuated alcohol-induced lipid metabolic disorders and oxidative damage. This provides a new strategy to promote the prevention and treatment of ALD.

Ameliorative effect of phenolic compound-pterostilbene on corticosterone-induced hepatic lipid metabolic disorder in broilers

The aim of this study was to investigate the ameliorative effects of pterostilbene (PTE), a polyphenolic compound, on stress-induced lipid metabolic disorders in the liver of broiler chickens. Six hundred healthy, one-day-old Arbor Acres (AA) with similar weight were randomly assigned to five groups, each consisting of 8 replicates with 15 broilers per replicate. The groups included: a control group (fed a basal diet), and four groups treated with corticosterone (CORT) at varying dietary levels of PTE supplementation: CORT (0 mg/kg PTE), CORT-PT200 (200 mg/kg PTE), CORT-PT400 (400 mg/kg PTE), and CORT-PT600 (600 mg/kg PTE). The results indicated that PTE administration to corticosterone (CORT)-injected broilers significantly improved weight gain, reduced liver index, and lowered the elevation of serum AST, GGT, Glu, TC, TG, and LDL-c concentrations induced by CORT injection (P < 0.05), but had no significant effect on serum CORT concentration (P > 0.05). PTE also significantly reduced the increased rate of abdominal fat deposition induced by CORT, decreased the average size of adipocytes, and downregulated the expression of the FAS gene (P < 0.05). It reversed the increase in liver TC, TG, LDL-c, and NEFA content induced by CORT (P < 0.05). PTE had no significant effect on the expression of the glucocorticoid receptor GR (P > 0.05), but significantly upregulated the protein expression of Sirt1 and p-AMPK (P < 0.05), promoted the expression of lipid autophagy genes MAP1LC3B and lipolytic genes LPL, but inhibited the expression of fatty acid synthesis genes SREBP-1c, ACC, and SCD (P < 0.05). The addition of PTE to the diet alleviated CORT-induced oxidative stress and inflammation by enhancing T-SOD and GSH-Px activities, reducing MDA content, inhibiting p-NF-κB p65 and NLRP3 expression and the release of TNF-α and IL-1β in the serum, and increasing IL-4 content (P < 0.05). Overall, dietary PTE effectively regulates lipid metabolism and antioxidant status, offering a potential strategy to mitigate stress-induced metabolic disruptions in broilers.

A charge reversal nano-assembly prevents hepatic steatosis by resolving inflammation and improving lipid metabolism

Lipid metabolism imbalance combined with over-activated inflammation are two key factors for hepatic stestosis. However, on-demand anchoring inflammation and lipid metabolism disorder for hepatic stestosis treatment has yet to be realized. Here we propose a charge reversal fullerene based nano-assembly to migrate hepatic steatosis via inhibiting macrophage-mediated inflammation and normalizing hepatocellular lipid metabolism in obesity mice. Our nano-assembly (abbreviated as FPPD) is comprised of electropositive polyetherimide (PEI), charge-shielded dimethylmaleic anhydride (DMA), and poly(lactic-co-glycolic acid) (PLGA), which provides hydrophobic chains for self-assembly with anti-oxidative dicarboxy fullerene poly(ethylene glycol) molecule (FP). The obtained FPPD nano-assembly owns a charge reversal ability that switches to a positive charge in an acidic environment that targets the electronegative mitochondria both in pro-inflammatory macrophages and steatosis hepatocytes. We demonstrate that the anti-oxidative and mitochondria-targeting FPPD notably reduces inflammation in macrophages and lipid accumulation in hepatocytes by quenching excessive reactive oxygen species (ROS) and improving mitochondrial function in vitro. Importantly, FPPD nano-assembly reveals a superior anti-hepatic steatosis effect via migrating inflammation and facilitating lipid transport in obesity mice. Overall, the charge reversal nano-assembly reduces over-activated inflammation and promotes lipid metabolism that provides an effectiveness of a multi-target strategy for hepatic steatosis treatment.

Integrated Multi-Omics Analyses Reveal Lipid Metabolic Signature in Osteoarthritis

Osteoarthritis (OA) is the most common degenerative joint disease and the second leading cause of disability worldwide. Single-omics analyses are far from elucidating the complex mechanisms of lipid metabolic dysfunction in OA. This study identified a shared lipid metabolic signature of OA by integrating metabolomics, single-cell and bulk RNA-seq, as well as metagenomics. Compared to the normal counterparts, cartilagesin OA patients exhibited significant depletion of homeostatic chondrocytes (HomCs) (P=0.03) and showed lipid metabolic disorders in linoleic acid metabolism and glycerophospholipid metabolism which was consistent with our findings obtained from plasma metabolomics. Through high-dimensional weighted gene co-expression network analysis (hdWGCNA), weidentified PLA2G2A as a hub gene associated with lipid metabolic disorders in HomCs. And an OA-associated subtype of HomCs, namely HomC1 (marked by PLA2G2A, MT-CO1, MT-CO2, and MT-CO3) was identified, which also exhibited abnormal activation of lipid metabolic pathways. This suggests the involvement of HomC1 in OA progression through the shared lipid metabolism aberrancies, which were further validated via bulk RNA-Seq analysis. Metagenomic profiling identified specific gut microbial species significantly associated with the key lipid metabolism disorders, including Bacteroides uniformis (P<0.001, R=-0.52), Klebsiella pneumonia (P=0.003, R=0.42), Intestinibacter_bartlettii (P=0.009, R=0.38), and Streptococcus anginosus (P=0.009, R=0.38). By integrating the multi-omics features, a random forest diagnostic model with outstanding performance was developed (AUC=0.97). In summary, this study deciphered the crucial role of a integrated lipid metabolic signature in OA pathogenesis, and established a regulatory axis of gut microbiota-metabolites-cell-gene, providing new insights into the gut-joint axis and precision therapy for OA.

The Association between High-density Lipoproteins and Periodontitis.

Periodontitis is one of the most typical chronic dental diseases. This inflammatory disease can change various functions of immune cells and impair lipid metabolism through proinflammatory cytokines. High-Density Lipoprotein (HDL) is considered protective of the cardiovascular system. It has anti-thrombotic and anti-inflammatory effects. In this article, we have reviewed the association between periodontitis and HDL. Various studies have demonstrated a reverse relationship between inflammatory cytokines and HDL. HDL contains antioxidative enzymes and proteins, whereas periopathogens impair HDL's antioxidant function. The presence of periodontal bacteria is associated with a low HDL level in patients with periodontitis. Genetic variants in the interleukin- 6 (IL)-6 gene and cytochrome (CYP)1A1 rs1048943 gene polymorphism are associated with HDL levels and periodontal status. Studies showed that HDL levels improve after treatment for periodontitis. On the one hand, periodontal pathogenic bacteria and their metabolites and pro-inflammatory cytokines from periodontal infection can result in various disorders of lipid metabolism and lipid peroxidation. On the other hand, hyperlipidemia and lipid peroxidation stimulate proinflammatory cytokines, resulting in oxidative stress and delayed wound healing, making individuals susceptible to periodontitis.

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

Recent investigations have revealed the tight connections between carboxylesterase (CE) and the lipid metabolism-associated disorders. In this work, based on the previous reports, a photoacoustic (PA) probe Hcy-CE was developed for the in vivo imaging of CE in two lipid metabolism disorders. The reaction with CE led to the departure of the carbamate quencher together with the linkage, thus to release of the reporter Hcy to exhibit the turn-on signals of PA reporting accompanied with the absorbance and fluorescence modes. The responses in all three modes showed high consistency. In the PA mode, the linear correlation range was CE level 0–10 U/L, while the limit of detection value was 0.52 U/mL. The optical performance of the probe Hcy-CE in the solution system was practical with high steadiness and selectivity. Moreover, Hcy-CE exhibited potential capability of monitoring the CE level in the induced foam cells. In particular, Hcy-CE realized the in vivo imaging of the CE level from multiple views and continuous cross-sections in the model mice of different groups. The combination of the PA imaging with the blood biochemical tests and immunohistochemically staining methods might help distinguish the three statuses of different mice from each other. This work provided meaningful information for the accurate diagnosis and regulation of the lipid metabolism-related disorders.

Hepatoprotective Effects of Rheum turkestanicum Janisch on High-fat Diet-induced Non-alcoholic Fatty Liver Disease in Mice

Background: Consumption of a high-fat diet (HFD) is one of the main causes of nonalcoholic fatty liver disease (NAFLD), which is increasing due to lifestyle changes and is still an important global health issue. Despite the efforts, there is still no common treatment for this disease. Studies have shown that the root of Rheum turkestanicum Janisch has a hypolipidemic effect and a significant antioxidant effect on liver tissue in diabetic rats. However, no experimental study has been performed on the hepatoprotective effects of this herb on HFD-induced NAFLD have been proven. background: Consumption of a high-fat diet (HFD) is one of the main causes of non-alcoholic fatty liver disease (NAFLD), which is increasing due to lifestyle changes and is still an important global health issue. Despite the efforts, there is still no common treatment for this disease. Studies have shown that the root of Rheum turkestanicum Janisch has a hypolipidemic effect and a significant antioxidant effect on liver tissue in diabetic rats. However, no experimental study has been performed on which the hepatoprotective effects of this herb on HFD-induced NAFLD have been proven. Objective: This study aimed to evaluate the effect of Rheum turkestanicum Janisch extract (RTE) on HFD-induced NAFLD in BALB/c mice. Materials and Methods: The study was performed with two models of prevention and therapeutic effect of RTE. Serum biochemical markers, histopathology, oxidative stress indicators, and qRTPCR were measured to evaluate the effects of RTE on lipid metabolism disorders in mice feeding with HFD. Results: In the prevention model, compared to the HFD group, RTE treatment decreased the levels of glucose, triglyceride, and cholesterol and improved liver profile markers, oxidative stress, and expression of genes involved in lipid metabolism. Conclusion: The results of this study suggest that RTE has hepatoprotective effects against HFDinduced liver damage by reducing oxidative stress, lipogenesis, and increasing beta-oxidation of free fatty acids.

Are Hyperlipidaemia and Insulin Resistance Risks For Sarcopenia?

To investigate whether insulin resistance and lipid metabolism disorders could be associated with sarcopenia. Cross-sectional descriptive study. Place and Duration of the Study: Department of Physical Medicine and Rehabilitation, Sanliurfa Training and Research Hospital, Sanliurfa, Turkiye, from December 2023 and May 2024. The study included 135 patients who met the inclusion and exclusion criteria. Data such as age, gender, body mass index (BMI), lipid profile, fasting blood glucose, C-peptide, and insulin levels were collected. Following sarcopenia screening, participants were divided into two groups for further examination, and the correlation between sarcopenia and other parameters was assessed. BMI levels were significantly higher in the sarcopenia group (p = 0.003). Triglyceride levels were also significantly elevated in the sarcopenia group (p = 0.001). The number of patients with dyslipidaemia in the sarcopenia group was higher compared to the non-sarcopenia group (p = 0.003). Correlation analysis revealed a positive association between sarcopenia and BMI, insulin resistance, high triglyceride levels, and the presence of dyslipidaemia (p = 0.002, p = 0.032, p = 0.002, p = 0.004, respectively). This study suggests that high triglyceride levels may represent a risk factor associated with sarcopenia and that sarcopenia may be associated with conditions such as high BMI, insulin resistance, and dyslipidaemia. Controlling lipid levels could be beneficial in reducing the risk of sarcopenia. Chronic disease, Hyperlipidaemia, Hypertriglyceridaemia, Insulin Resistance, Sarcopenia.

EPA but not DHA Prevents Lipid Metabolism Disorders by Regulating Myogenic IL-6 in High-fat fed mice

EPA but not DHA Prevents Lipid Metabolism Disorders by Regulating Myogenic IL-6 in High-fat fed mice

Anti-b diminishes hyperlipidaemia and hepatic steatosis in hamsters and mice by suppressing the mTOR/PPARγ and mTOR/SREBP1 signalling pathways.

As a chronic metabolic syndrome, hyperlipidaemia is manifested as aberrantly elevated cholesterol and triglyceride (TG) levels, primarily attributed to disorders in lipid metabolism. Despite the promising outlook for hyperlipidaemia treatment, the need persists for the development of lipid-lowering agents with heightened efficiency and minimal toxicity. This investigation aims to elucidate the lipid-lowering effects and potential pharmacodynamic mechanisms of Anti-b, a novel low MW compound. We employed high-fat diet (HFD) in hamsters and mice or oleic acid (OA) in cultures of HepG2 cells and LO2 cells to induce hyperlipidaemia models. We administered Anti-b to assess its therapeutic effects on dyslipidaemia and hepatic steatosis. We used western blotting, RNA sequencing, GO and KEGG analysis, oil red O staining, along with molecular docking and molecular dynamics simulation to elucidate the mechanisms underlying the effects of Anti-b. Anti-b exhibited a substantial reduction in HFD-induced elevation of blood lipids, liver weight to body weight ratio, liver diameter and hepatic fat accumulation. Moreover, Anti-b demonstrated therapeutic effects in alleviating total cholesterol (TC), TG levels, and lipid accumulation derived from OA in HepG2 cells and LO2 cells. Mechanistically, Anti-b selectively bound to the mTOR kinase protein and increased mTOR thermal stability, resulting in downregulation of phosphorylation level. Notably, Anti-b exerted anti-hyperlipidaemia effects by modulating PPARγ and SREBP1 signalling pathways and reducing the expression level of mSREBP1 and PPARγ proteins. In conclusion, our study has provided initial data of a novel low MW compound, Anti-b, designed and synthesised to target mTOR protein directly. Our results indicate that Anti-b may represent a novel class of drugs for the treatment of hyperlipidemia and hepatic steatosis.