Serum Lipid Metabolism Research Articles

Identification of novel serum lipid metabolism potential markers and metabolic pathways for oral cancer: a population-based study

ObjectiveThis study aims to identify potential lipid biomarkers and metabolic pathways associated with oral cancer (OC). Then to establish and evaluate disease classification models capable of distinguishing OC patients from healthy controls.MethodsA total of 41 OC patients and 41 controls were recruited from a hospital in Southeast China to examine the serum lipidomics by Ultra-high Performance Liquid Chromatography Q Exactive Mass Spectrometry (UHPLC-QE-MS).ResultsThe total serum lipid profile showed that triglycerides accounted for the highest proportion of total metabolites, reaching 35.90% of the total. A total of 74 different metabolites were screened (12 up-regulated and 62 down-regulated), mainly enriched in the glycerophospholipid metabolism pathway. The three most significant changes in lipid metabolites were phosphatidylcholine (PC(18:3e/17:2)), acylcarnitine (ACar(14:2)), and glucuronosyldiacylglycerol (GlcADG(14:1/14:1)). The disease classification model, constructed using a KNN algorithm with 13 metabolites selected through LASSO screening, achieved the best performance, with an AUC of 0.978 (0.955-1.000).ConclusionLipid metabolic biomarkers identified in this study exhibit potential as candidate biomarkers for OC diagnosis. Further validation through prospective studies is required to confirm their clinical utility in early detection.

High-selenium exposure is associated with modulation of serum lipid metabolism.

At present, there is no consensus on the relationship between selenium (Se) exposure and human serum lipid metabolism. The etiological role of high-Se exposure in lipid markers, dyslipidemia, and nonalcoholic fatty liver (NAFLD) remains unclear. We used serum untargeted metabolomics analysis to evaluate whether high-Se exposure is cross-sectionally associated with lipid metabolism in adults from high-Se exposure area (n = 112) and control area (n = 101) in Hubei Province, China. An untargeted liquid chromatography/mass spectrometry (LC/MS)-based metabolomic analysis identified 144 differential pathways and yielded 204 differentially abundant metabolites, including 32 lipid metabolites associated with lipids profiles. To further explore the correlation between Se exposure and serum lipid metabolism, we measured serum levels of lipid profiles among all the people, including serum cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (APOB). The average serum Se level of the high-Se exposure group was 537.18 μg/L, significantly higher than 72.98 μg/L in the control group (p < 0.0001). The measurement levels of serum TG, LDL-C, HDL-C, and APOB in the high-Se exposure group were 1.03 (0.76, 1.34) mmol/L, 2.25 ± 0.48 mmol/L, 1.12 ± 0.24 mmol/L, and 0.77 ± 0.15 g/L, respectively, while the control group were 1.13 (0.84, 1.80) mmol/L, 2.56 ± 0.61 mmol/L, 1.02 ± 0.22 mmol/L, and 0.83 ± 0.16 g/L, respectively (all p values <0.05). Correlation analysis showed a significant negative correlation between serum Se and CHOL (r = -0.201, p < 0.01), serum Se is also associated with metabolomics markers, the negative correlation includes glyceric acid and ect., the positive correlation includes phosphorylcholine and ect. Our study suggests that high-Se exposure is negatively associated with serum lipid profiles and decreases the risk of high-TC and HDL-C dyslipidemia.

Zhuyu pill attenuates metabolic-associated fatty liver disease by regulating macrophage polarization through TLR4 signaling pathway.

Metabolic-associated fatty liver disease (MAFLD) is the leading chronic liver disease globally, impacting a large segment of the population. The Zhuyu Pill (ZYP), a traditional Chinese remedy, has been clinically used for treating MAFLD, with its effectiveness demonstrated in both human patients and animal models. However, the underlying mechanisms of how ZYP addresses MAFLD still require further investigation. This study investigated the molecular mechanism of ZYP in treating MAFLD through both in vivo and vitro methods. A murine MAFLD model was induced by a high-fat, high-fructose diet for 12 weeks. ZYP was administered for 4 weeks, with fenofibrate serving as a positive control. Indicators of lipid metabolism in serum and liver tissue were detected by automatic biochemical analyzer and ELISA, respectively. Histopathological evaluation of liver sections was performed using HE and oil red O staining. Transcriptomics was employed to further investigate the therapeutic mechanism of ZYP in MAFLD. Additionally, macrophages and their polarization in the liver were analyzed using ELISA, flow cytometry, immunohistochemistry, and immunofluorescence (IF). Candidate proteins and pathways were validated in vivo and in vitro by western blotting and IF. Validation of the pathway was performed in vitro using inhibitors and co-culture strategies. ZYP significantly improved obesity and hepatic steatosis in MAFLD mice, reducing body/liver weight and regulating lipid metabolism indicators in serum and liver tissue. Bioinformatics analysis of transcriptomic data highlighted lipid metabolism regulation and inflammation control as key effects of ZYP in treating MAFLD. The in vivo experimental results showed that ZYP inhibited M1 polarization of macrophages (pro-inflammatory) and promoted M2 polarization of macrophages (anti-inflammatory) in MAFLD mice. Further in vivo and vitro experiments indicated that ZYP competes with LPS to bind to Toll-like receptor 4 (TLR4), suppressing M1 polarization in liver macrophages, and improving MAFLD. The in vitro co-culture system also confirmed that ZYP reduces liver lipid deposition by modulating M1 macrophage polarization. ZYP alleviates MAFLD by inhibiting M1 polarization of liver macrophages, indicating that ZYP may be a promising treatment for MAFLD. Its mechanism of action is to inhibit the TLR4/MyD88/TRAF6 signaling pathway, modulate macrophage polarization, and improve inflammatory response.

Morphological features of white adipose tissue in rats with different levels of energy metabolism in visceral obesity

Histomorphological changes of visceral white adipose tissue in obesity as a function of the level of energy metabolism in the body have not been sufficiently studied. The aim of this study was to investigate and compare the structural changes of visceral white adipose tissue in rats with different metabolic levels and severe visceral obesity. The study was carried out on male Wistar rats aged 3 months at the start of the experiment. Control animals received standard diet. Experimental rats were fed a high calorie diet for 12 weeks. At the end of the experiment, rats from both the control and experimental groups were divided into low and high level of energy metabolism depending on the intensity of total oxygen consumption. Histological preparations of visceral white adipose tissue were prepared according to the standard method. Histomorphometry was performed on digital images using the “Image J 1.34p” computer program. Biochemical methods were used to determine the concentration of triglycerides, lipids and cholesterol in blood serum. The method of multifrequency bioimpedance was used to assess the biophysical properties of visceral white adipose tissue. The data obtained were processed by methods of variational statistics using one-way analysis of variance. It was shown that long-term use of a high-calorie diet led to the development of visceral obesity, which was manifested by a significant increase in the weight of visceral fat and an increase in the concentration of indicators of lipid metabolism in blood serum. It was found that a high-calorie diet altered the morphological structure of the rat’s visceral white adipose tissue, leading to adipocyte hypertrophy, reduced blood volume and increased the amount of connective tissue in it. The bioelectrical properties of the visceral white adipose tissue changed, as evidenced by an increase in its electrical impedance and a decrease in its frequency dispersion coefficient. The intensity of structural, biochemical and biophysical changes in the visceral white adipose tissue was more pronounced in rats with low level of energy metabolism and depended on the degree of obesity. The results obtained are important for practical medicine in the development of new effective methods for the prevention and treatment of obesity in patients according to level of energy metabolism.

Study on the Mechanism of Bifidobacterium animalis subsp. lactis F1-3-2 Regulating Bile Acid Metabolism Through TMA-TMAO Pathway to Improve Atherosclerosis.

Atherosclerosis is a major cause of cardiovascular disease (CVD). The trimethylamine (TMA)-trimethylamine N-oxide (TMAO) pathway is a key crossover pathway highly associated with diet, gut microbiome, and atherosclerosis. The Bifidobacterium animalis subsp. lactis F1-3-2 (Bif. animalis F1-3-2, No. CCTCCM2020832) was screened through in vitro and in vivo experiments in the early stage of this study with excellent lipid-lowering and anti-inflammatory function. By building an atherosclerosis model and focusing on TMAO, the specific mechanism of Bif. animalis F1-3-2 to improve atherosclerosis was explored. The study found that Bif. animalis F1-3-2 effectively improved the accumulation of aortic plaque in atherosclerotic mice. The strain improved lipid metabolism in serum and liver. It decreased the serum TMA and TMAO, regulated bile acid composition, participated in the farnesoid X receptor (FXR) pathway to improve lipid metabolism, and further reduced the aortic macrophage foam cell accumulation. In addition, the strain could improve the structure of the intestinal microbiome and reduce the proportion of Firmicutes and Bacteroidetes. The abundance of Turicibacter, Clostridium sensu stricto_1, and Romboutsia was reduced at the genus level. The differential microbiota is highly correlated with bile acid metabolism, which is speculated to be involved in ameliorating atherosclerotic lipid metabolism disorders.

Vitamin D supplementation alleviates high fat diet-induced metabolic associated fatty liver disease by inhibiting ferroptosis pathway.

Recently, a significant negative correlation has been found between vitamin D (VD) and metabolic associated fatty liver disease (MAFLD), suggesting a potential beneficial role of VD in preventing of MAFLD, while underscoring the importance of exploring its mechanisms. The experiment comprised two parts: male C57BL/6J mice (6 weeks) were fed a high-fat diet (HFD) and intraperitoneally injected with vitamin D3 (VD3) (1.68 IU/g/week) for 16 weeks. Meanwhile, palmitic acid (PA)-induced HepG2 cells were treated with 1,25(OH)2D3 (10 nM). The general conditions of the mice were evaluated by measuring body weight, liver/body weight, serum biochemical parameters, and inflammation indices. Additionally, injury-associated indices and histopathology were used to assess the severity of liver injury. Furthermore, indicators of ferroptosis, including lipid peroxidation, iron aggregation, and the aberrant expression of related proteins, were determined using Prussian blue staining, ELISA assay, and Western blot. Long-term VD3 administration significantly reduced body weight gain and the liver/body weight ratio of HFD-induced MAFLD mice, while also improving serum lipid metabolism dysregulation and enhancing insulin sensitivity. The changes in the expressions of liver injury indices and histological manifestations due to VD3 treatment indicated that VD3 may exerts beneficial effects on liver injury through inhibiting inflammatory cell infiltration and vacuolation. Importantly, VD3 supplementation also inhibited ferroptosis by enhancing the body's antioxidant capacity, reducing local iron aggregation, and modulating the expression levels of ferroptosis-related proteins. These findings were further confirmed in a PA-induced HepG2 steatosis cell model, highlighting the pharmacological effects of VD. VD shows promise in mitigating HFD -induced liver injury by improving metabolic dysregulation and inhibiting ferroptosis, suggesting therapeutic potential in MAFLD.

Oxidative Status and Lipid Metabolism Analytes in Dogs with Mast Cell Tumors: A Preliminary Study.

Mast cell tumors (MCTs) are common skin neoplasms in dogs. Prognostic indicators include histologic grade, clinical stage, high Ki-67 index, elevated argyrophilic nucleolus organizer regions (AgNOR) index, c-kit mutations, and recurrence after surgery. Blood serum redox status has been shown to correlate with prognostic factors in canine lymphoma and mammary tumors. This study aimed to assess the correlation between established prognostic factors and serum redox status and lipid metabolism analytes in dogs with MCTs. Dogs with cutaneous (n = 33) or subcutaneous (n = 6) MCTs, without comorbidities, were studied. Staging was evaluated based on cytology of regional lymph nodes and ultrasound-guided liver and spleen aspiration cytology. Histologic grading and immunohistochemical staining for Ki-67 and KIT patterns were performed on excised tumor specimens. Dogs were categorized by Patnaik grading (1-3), Kiupel grading (low/high), metastatic status, Ki-67 positive nuclei per cm2 (>23 or ≤23), and KIT pattern (I, II-III). Paraoxonase-1, Butyrylcholinesterase, Cupric Reducing Antioxidant Capacity (CUPRAC), Diacron Reactive Oxygen Metabolites (d-ROMs), and oxy-adsorbent levels were measured before any therapeutic intervention. ANOVA and independent t-tests were used to detect differences in the mean values among groups. Paraoxonase-1 activity was significantly lower in Patnaik grade 3 (p = 0.003) and Kiupel high-grade (p = 0.022) MCTs. No significant differences were found in CUPRAC, d-ROMs, or oxy-adsorbent levels across different prognostic groups. This study found a significant correlation between histologic grading and Paraoxonase-1 activity, suggesting a potential role of Paraoxonase-1 as a prognostic biomarker in canine MCTs.

Synergistic Effect and Mechanism of Combined Astaxanthin and Curcumin Administration on Ovarian Function in PCOS Mice.

To investigate the synergistic effect of astaxanthin and curcumin on ovarian function in polycystic ovary syndrome (PCOS) mice and to elucidate the underlying mechanisms, fifty 4-week-old female mice were randomly divided into five groups: (i) normal control group; (ii) PCOS model group; (iii) PCOS + astaxanthin group; (iv) PCOS + curcumin group; and (v) PCOS + astaxanthin-curcumin. Throughout the study, various parameters were meticulously evaluated, including serum levels of key reproductive hormones (testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH)), as well as monitoring alterations in the estrous cycle, follicle development, and ovulation rates. Additionally, markers of oxidative stress and inflammation were measured. Findings revealed that PCOS mice exhibited disordered estrous cycle, polycystic ovarian morphologies, abnormal serum reproductive hormones and lipid metabolism, heightened oxidative stress, and augmented inflammatory responses. Notably, upon administration of the combined astaxanthin and curcumin, PCOS mice exhibited significant improvements in their estrous cyclicity and ovarian histology. The treatment led to a significant reduction in serum total cholesterol (TC) levels and normalization of T, E2, FSH, LH, and AMH levels. Moreover, there was a marked decrease in the levels of serum reactive oxygen species (ROS) and malondialdehyde (MDA), indicating attenuation of oxidative stress. Concurrently, the activity of the antioxidant enzyme catalase (CAT) significantly increased, while proinflammatory cytokines interferon-γ (IFN-γ) and interleukin-6 (IL-6) in the ovarian tissue were notably decreased. The combined treatment also resulted in a substantial increase in the number of ova and a significant decline in the rate of abnormal ova, with these therapeutic effects proving more effective compared to either astaxanthin or curcumin alone. In conclusion, the co-administration of astaxanthin and curcumin demonstrated a remarkable effect in improving abnormal lipid metabolism and restoring reproductive endocrine functions in PCOS mice. Furthermore, it effectively mitigated systemic and local oxidative stress and chronic inflammatory injury, thereby promoting follicular growth and enhancing ovulatory function in the context of PCOS.

Chiglitazar ameliorates dehydroepiandrosterone-induced polycystic ovary syndrome in rats

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder accompanied by ovulatory dysfunction. Insulin resistance (IR) is a key pathogenic mechanism in PCOS, and insulin sensitizers, such as metformin and pioglitazone, can improve PCOS symptoms. Chiglitazar, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is also an insulin sensitizer; however, its therapeutic effects have not yet been studied in PCOS. We evaluated the therapeutic effects of chiglitazar in a rat model of PCOS.MethodsSprague–Dawley rats aged 4 weeks were injected subcutaneously with dehydroepiandrosterone (DHEA) (6 mg/100 g/day) to establish PCOS, and a control (CON) group was established. The rats were divided into the CON, PCOS model (DHEA), pioglitazone-treated (DHEA + PIO), and chiglitazar-treated (DHEA + CHI) groups. The DHEA + PIO group received pioglitazone (20 mg/kg/day) and the DHEA + CHI group received chiglitazar (20 mg/kg/day), each for 15 days. Body weight, estrous cycle, and glucose tolerance test (GTT) and insulin resistance test (ITT) results were monitored. Experimental animal energy metabolism systems were utilized to assess metabolic parameters. Enzyme-linked immunosorbent assay was conducted to detect changes in serum hormones, including insulin, adiponectin, sex-related hormones, and lipid metabolism indicators. The ovaries were used for molecular biology experiments to detect changes in Akt/phosphorylated Akt and glucose transporter 4 (GLUT4) expression by Western blotting and quantitative polymerase chain reaction.ResultsChiglitazar and pioglitazone improved PCOS symptoms. However, chiglitazar demonstrated a more pronounced effect on lipid improvement and weight gain than pioglitazone. In the DHEA + PIO and DHEA + CHI groups, there was notable recovery in oxygen consumption and carbon dioxide output; substantial improvement in GTT and ITT results; an increase in adiponectin; and a reduction in serum insulin, androgens, luteinizing hormone (LH), and LH/follicle-stimulating hormone ratio. Compared with the DHEA group, the DHEA + CHI group exhibited notable decreases in triglycerides, free fatty acids, and atherosclerosis index, while the DHEA + PIO group demonstrated no changes. Granulosa cells and healthy follicles increased in ovarian sections. Ovarian steroidogenic enzymes also increased in the DHEA + PIO and DHEA + CHI groups compared with the DHEA group. Mechanistically, chiglitazar increased Akt phosphorylation.ConclusionChiglitazar significantly improved ovulation in rats with PCOS and may be a potential novel therapeutic strategy for PCOS.

Age-related features of the main risk factors and clinical and laboratory parameters in men aged 30–50 years with atherothrombotic stroke

Introduction. Ischemic stroke in patients under 50 years of age is not uncommon. The prevalence of stroke in young people increases due to the increase in risk factors. Early detection of risk factors and optimization of primary and secondary preventive therapy are mandatory to reduce the burden of stroke in young people and preserve potential years of life.Objective. To identify and evaluate the main risk factors and clinical and laboratory parameters in men aged 31–40 and 41–50 years with atherothrombotic stroke.Material and methods. Before the development of the COVID-19 pandemic, 60 patients were examined (mean age 43.3±3.8 years). All patients underwent neuroimaging of the brain, ultrasound examination of the main vessels of the head, echocardiography, ECG, and laboratory analysis of blood serum.Results. Among all patients, there were 10 patients aged 31–40 years (mean age 37.4±2.6 years) and 50 patients aged 41–50 years (mean age 44.5±2.8 years). All patients had atherosclerotic lesions of the main arteries of the head, with stenosis of more than 70 % only in patients aged 41–50 years. Among patients aged 31–40 years and 41–50 years, the most common risk factors were arterial hypertension (90 and 72 %), smoking (70 and 72 %), dyslipidemia (66.7 and 60 %), and regular alcohol consumption (30 and 36 %). The study showed statistically significant correlations of the main vascular risk factors with serum lipid metabolism indices, hemostasis and endothelial dysfunction markers.Conclusions. The study showed the frequency of occurrence of the main risk factors in patients with atherothrombotic stroke aged 31–40 and 41–50 years, as well as the role of lipid metabolism disorders, hemostasis disorders and endothelial dysfunction in their development.

Anti-inflammatory mechanism of Houttuynia cordata polysaccharides against ulcerative colitis based on multi-omics conjoint analysis

The Houttuynia cordata polysaccharide (HCP) was extracted from the traditional Chinese medicine, Houttuynia cordata, known for its anti-inflammatory properties. It has an acidic heteropolysaccharide with a molecular weight of approximately 13.38 kDa, consisting of 7 monosaccharides such as galactose, galacturonic acid, and glucose. Mouse ulcerative colitis (UC) model experiments demonstrated its effective anti-inflammatory activity at concentrations of 100 mg/kg and 300 mg/kg respectively. The objective of this study was to investigate the mechanism of action underlying the therapeutic effects of HCP in UC through omics analysis method. A total of 724 different metabolites and 246 differential lipids were identified. Through metabolomic analysis, six metabolic pathways including the linoleic acid metabolic pathway, caffeine metabolic pathway, mannose and fructose metabolic pathways, methyl histidine metabolic pathway and fatty acid biosynthesis, which were significantly associated with colon-related diseases. Subsequently, lipidomics analysis revealed that the metabolic pathways of α-linolenic and linoleic acid, fatty acid biosynthesis, and glycerolipid metabolism exhibited significant associations with serum lipid metabolism. These findings suggested that HCP had potential therapeutic effects in treating UC.

Effects of Soluble and Insoluble Fibre on Glycolipid Metabolism and Gut Microbiota in High-Fat-Diet-Induced Obese Mice.

Dietary fibre can alleviate or reduce the risk of obesity and obesity-induced abnormalities in glycolipid metabolism. However, the effects of different types of dietary fibre or their combinations on obesity remain unclear. Here, we explored the effects of different ratios of inulin soluble dietary fibre (ISDF) and barley leaf insoluble dietary fibre (BLIDF) on the body weight, glycolipid metabolism and gut microbiota of obese mice. Seven experimental groups were treated with different combinations of soluble and insoluble fibre, comprising HFD (high-fat diet without dietary fibre), BLIDF, ISDF, I3S1DF (insoluble/soluble = 3:1), I2S2DF (insoluble/soluble = 1:1), I1S3DF (insoluble/soluble = 1:3) and MIX (inulin, BLIDF and matcha powder fibre; insoluble/soluble = 3.6:1) groups. Our results showed that the BLIDF, ISDF and MIX treatments decreased the body weight gain of the HFD mice significantly after eight-week interventions. All the fibre intervention groups except the MIX group displayed lower fasting blood glucose and glycosylated serum protein levels than the HFD group. BLIDF, ISDF, I3S1DF and I2S2DF improved the glucose tolerance of the mice. Moreover, none of the dietary fibre interventions affected the liver lipid metabolism, while I3S1DF and I1S3DF improved the abnormal serum lipid metabolism. BLIDF, ISDF, I3S1DF and I2S2DF reduced the serum IL-6 levels, and BLIDF and I1S3DF increased SOD activity significantly. Additionally, all the dietary fibre interventions decreased the Firmicutes to Bacteroidota (F/B) ratio and increased the abundance of beneficial gut microbes differently. In short, our results suggest that different ratios of soluble and insoluble dietary fibre have unique impacts on mice body weight, glycolipid metabolism, inflammation and gut microbiota. The ratio of soluble to insoluble dietary fibre intake should be considered for specific health goals in the future.

Study of carbonate alkalinity-induced hepatic tissue damage in Hefang crucian carp (Carassius auratus) based on transcriptomic analysis

This study investigated the effects of different sodium bicarbonate (NaHCO3) concentrations (0 g/L, 1 g/L, and 3 g/L) on Hefang crucian carp (12.0 ± 1.1 g) over a 96-hour period. The experiment is divided into three groups, each with three replicates, and each replicate contains 30 fish. We employed a comprehensive approach integrating histology, physiological and biochemical assays, transcriptomics, as well as artificial intelligence (AI)-assisted analysis. This multifaceted method allowed us to examine changes in gill and liver morphology, osmoregulation, antioxidant capacity, immune response, and physiological metabolism. Results showed that gill and liver tissue damage increased with rising water alkalinity. Serum sodium (Na+), potassium (K+), blood ammonia, and gill Na+/K+-ATPase (NKA) levels increased significantly (p < 0.05). Hepatic antioxidant enzymes initially increased, then decreased with prolonged stress. Serum and liver immunoenzyme indices were higher in bicarbonate-treated groups compared to controls. Carbonate treatment altered lipid and glucose metabolism in both serum and liver. Transcriptome analysis, enhanced by large language models (LLMs), revealed differentially expressed genes (DEGs) significantly associated with ion binding, transport, apoptosis, and metabolism. In conclusion, excessive carbonate intake in fish alters serum physiological functions and affects hepatic metabolic functions. Crucian carp primarily regulate hepatic antioxidant systems, utilize carbohydrate breakdown for energy requirements, and employ lipids in osmoregulation. This study provides insights into fish adaptation to saline-alkaline environments and offers support for the development of aquaculture in saline-alkaline waters.

Lipid metabolism disorders and albuminuria risk: insights from National Health and Nutrition Examination Survey 2001–2018 and Mendelian randomization analyses

Background Previous studies have revealed an underlying connection between abnormal lipid metabolism and albuminuria. We aim to investigate the causal relationship between lipid metabolism disorders and the risk of albuminuria from both a population and genetic perspective. Methods A cross-sectional study was conducted by using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Multivariable-adjusted logistic regression, subgroup analysis, interaction tests and restricted cubic spline (RCS) were employed statistically. Mendelian randomization (MR) analysis was performed to validate the causal relationship between exposure and outcome to mitigate confounding factors and reverse causation interference. Results After adjusting for confounders, HDL levels (1.03-2.07 nmol/L) were associated with a reduced risk of albuminuria. In contrast, elevated cholesterol levels (>6.2 nmol/L) and triglyceride levels (>2.3 nmol/L) were associated with an increased risk of albuminuria. Serum triglyceride concentration emerged as a potential risk factor for albuminuria. In MR analysis, a reduced risk of albuminuria was associated with serum total HDL level (IVW: OR = 0.91, 95% CI = 0.86-0.97, p = 0.002). In contrast, cholesterol esters in medium VLDL (IVW: OR = 1.05, 95% CI = 1.00-1.10, p = 0.032), chylomicrons and extremely large VLDL (IVW: OR = 1.08, 95% CI = 1.03-1.14, p = 0.003), and triglycerides (IVW: OR = 1.14, 95% CI = 1.09-1.19, p < 0.001) were associated with an increased risk of albuminuria. Conclusion A causal relationship exists between serum lipid metabolism disorder and albuminuria risk. Further validation of additional blood lipid metabolism biomarkers is imperative for future studies.

The Impact of Acute Ammonia Nitrogen Stress on Serum Biochemical Indicators and Spleen Gene Expression in Juvenile Yellowfin Tuna (Thunnus albacares).

The presence of ammonia nitrogen in water has a significant impact on the serum and spleen of fish, potentially leading to changes in substances such as proteins in the serum while also causing damage to the immune function of the spleen. To investigate the effects of ammonia nitrogen (NH3-N) stress on juvenile yellowfin tuna (Thunnus albacares), this study established three NH3-N concentrations, 0, 5, and 10 mg/L, denoted as L0, L1, and L2, respectively. Serum and spleen samples were collected at 6, 24, and 36 h. The effects of different NH3-N concentrations and exposure times on the physiological status of juvenile fish were investigated by analyzing serum biochemical indices and splenic gene expression. The results indicate that in the L1 group, the serum high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), complement 3 (C3) and complement 4 (C4) levels, and acid phosphatase (ACP) activity showed a trend of initially increasing and then decreasing. In the L2 group, the serum low-density lipoprotein cholesterol (LDL-C), HDL-C, and C4 levels and ACP activity also displayed an initially rising and then declining trend, while TG, C3, and creatinine (CRE) levels and alkaline phosphatase (AKP) activity showed an upward trend. In the L1 group, glutathione peroxidase 1b (GPX1b), interleukin 10 (IL-10), interleukin 6 receptor (IL-6r), and tumor necrosis factor alpha (TNF-α) gene expression levels in the spleen exhibited a trend of first increasing and then decreasing. In the L2 group, IL-10, IL-6r, tumor necrosis factor beta (TNF-β), caspase 2 (casp2), and caspase 9 (casp9) gene expression levels in the spleen also showed an initial increase followed by a decrease. When NH3-N levels are below 5 mg/L, it is recommended to limit stress exposure to no more than 36 h for the juvenile fish. For concentrations ranging from 5 to 10 mg/L, stress should be strictly controlled to within 24 h. Exposure to high NH3-N levels may affect biochemical indicators such as serum lipid metabolism, immunity, and metabolism in juvenile fish, and may damage the expression of antioxidant, immune gene, and apoptosis factors in the spleen. This study aims to deepen our understanding of the effects of NH3-N on juvenile tuna, with the goal of establishing effective water quality monitoring and management strategies. This will ensure the quality of aquaculture water, reduce the harm caused by NH3-N to juvenile yellowfin tuna, and enhance aquaculture efficiency and product quality.

Effects of dietary metabolizable energy and crude protein levels on laying performance, egg quality and fecal microbiota of Taihe Silky Fowl during the peak laying period.

The experiment aimed to study the effect of dietary metabolizable energy (ME) and crude protein (CP) on laying performance, egg quality, serum routine biochemical and lipid metabolism indicators, the apparent digestibility of nutrients, and fecal microbiota of Taihe Silky Fowl (TSF) during the peak laying period. A total of 540 26-week-old TSF female fowls were randomly allocated to 9 groups with 5 replicates per group and 12 fowls per replicate. The fowls were fed with a 3 × 3 factorial arrangement of treatments diets (ME:10.88,11.30, or 11.72 MJ/kg; CP: 15, 16, or 17%). With the increasing CP level, the egg weight (EW) (P=0.023), egg production (EP) (p=0.047), and egg mass (EM) (p=0.022) enhanced, while the feed conversion rate (FCR) (p=0.023) decreased. As the ME levels grew, the average daily feed intake (ADFI) (p<0.001) and FCR (p=0.045) decreased. With enhanced ME, the triglycerides (TG) (p=0.037), total cholesterol (TCHO) (p=0.041), and high-density lipoprotein cholesterol (HDL-C) (p=0.028) increased, whereas the low-density serum lipoprotein cholesterol (LDL-C) (p=0.039) decreased. The apparent digestibility of crude protein increased as the ME level increased (p= 0.029) and as the CP level decreased (p=0.027). At the same time, the apparent digestibility of gross energy increased as the ME level increased (p=0.018). Different levels of ME or CP changed the composition of fecal microbiota, 17% CP increased the abundance of Bifidobacterium. It is suggested that 10.88 MJ/kg dietary ME and 17% CP level are suitable for the nutritional requirements of TSF during the peak laying period.

The Effects of Multiple Acute Turkesterone Doses on Indirect Measures of Hypertrophy and Metabolic Measures: A Preliminary Investigation

Turkesterone is a naturally occurring plant steroid touted for its medicinal, pharmacological, and biological properties with no reported adverse side effects compared with traditional anabolic androgenic steroids (AAS). However, this ostensible enhancement to increase muscle protein synthesis and facilitate augmented thermogenesis remains undescribed despite uninformed and potentially haphazard consumption. To investigate whether turkesterone enhances insulin-like growth factor-1 (IGF-1) and resting metabolic rate (RMR), eleven apparently healthy males (23.3 ± 2.2) volunteered to participate in the present study with samples collected pre-, 3H post-, and 24H post-ingestion. Subsequent analyses failed to reveal any significant main condition, time, or interaction main effects for serum IGF-1, RMR, lipid, and carbohydrate metabolism (p &gt; 0.05). However, non-significant serum IGF-1 concentrations increased with both turkesterone conditions and remained elevated when compared with placebo. Similarly, RMR remained elevated above baseline across the 3 h assessed. Although these data fail to fully support turkesterone as a potent anabolic supplement, nevertheless, our findings are foundational to persistently tease apart this supplement’s purported ergogenic effects and underscore its favorable hemodynamic and gastrointestinal tolerability profile. Future investigations should, therein, aim to assess turkesterone-mediated IGF-1 increases on long-term whole-muscle growth across several training sessions to further substantiate its efficacy on anabolism.

Anemarrhena asphodeloides Bunge total saponins lower lipid via modulating MAOA activity to enhance defense mechanisms in mice and C. elegans

Ethnopharmacological relevanceWithin Anemarrhena asphodeloides Bunge (AAB), the pivotal bioactive constituents are identified as Anemarrhena asphodeloides Bunge total saponins (ABS). In traditional pharmacology, ABS has exhibited notable anti-inflammatory, hypoglycemic, and cardioprotective properties. Despite these observed effects, the specific protective mechanisms of ABS against metabolic diseases and improving the endocrine system remain largely uncharted. Aim to studyThis work intends to shed light on the effects and intrinsic mechanisms of ABS on metabolic diseases. Materials and methodsThe characterization of ABS components was achieved through High-Performance Liquid Chromatography/Mass Spectrometry (HPLC/MS). To evaluate ABS's anti-inflammatory efficacy, mouse macrophages underwent analysis using the Griess method. Induced differentiation of mouse fibroblasts was assessed through Oil Red O staining. In an obesity model with C57BL/6 N mice, ABS administration prompted measurements of glucose and insulin tolerance. Western blot analysis quantified lipolysis and anti-inflammatory protein expression. Nile red staining gauged body fat content in C. elegans post-ABS treatment. The mechanism of ABS action was elucidated through mRNA sequencing, further validated using RNA interference technology, and nematode mutants. ResultsABS showcased the ability to diminish Nitric Oxide (NO) production in inflammatory macrophages and shrink adipocyte lipid droplets. In mice experiments, ABS was effective in alleviating fat accumulation and affecting serum lipid metabolism in diabetic mice. It enhanced oral glucose tolerance and insulin tolerance while increasing lipolysis-associated protein expression. ABS notably reduced fat content in C. elegans. Mechanistically, ABS downregulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and monoamine oxidase A (MAOA) expression while enhancing UGT, ilys-2, and ilys-3. Lipolysis emerged as a pivotal pathway for ABS in the therapeutic intervention of metabolic diseases. ConclusionsOur investigation has revealed that ABS exert a role in combating metabolic diseases by enhancing the body's defense mechanisms. ABS activate the NLRP3-neurotransmitter-visceral adipose pathway in mice, thereby bolstering resistance and diminishing fat accumulation. In C. elegans, ABS downregulated the expression of MAOA, bolstered resistance, and augmented glucuronidase activity, consequently leading to a reduction in fat content.

Transcriptome, histology, and enzyme activities analysis of liver in Phoxinus lagowskii to the low temperature stress and recovery

Assessing the response and resilience of fish to low temperatures over different time scales can provide valuable insights into their mechanisms of adaptation to cold conditions. Farmed Amur minnows (Phoxinus lagowskii) frequently encounter low temperatures, especially during winter. However, the specific responses of P. lagowskii to low-temperature stress remain largely unexplored. In this study, we examined serum glucose and cortisol levels, histological changes, enzymes associated with phosphate and carbohydrate metabolism, triglyceride levels, and liver transcriptomics under various conditions: control (CK), short-term cold exposure (6 days, SC), prolonged cold exposure (14 days, PC), and recovery (RY) from cold exposure at 2 °C. Liver vacuolation was observed during short-term cold exposure. Additionally, we analyzed the enzymatic activity related to carbohydrate and lipid metabolism in serum and liver. Liver transcriptomic data revealed that the PPAR signaling pathway and autophagy-related genes were enriched during short-term cold exposure. Carbohydrate metabolism-related pathways, including the AMPK and MAPK signaling pathways, were significantly enriched after prolonged cold exposure. Metabolic pathways such as fat digestion and absorption, glycine, serine, and threonine metabolism, and arginine and proline metabolism were significantly enriched in the recovery group. Rapid warming after prolonged cold stress allowed P. lagowskii to recover quickly. These findings suggest that P. lagowskii has a strong adaptive capacity for energy metabolism during prolonged cold exposure and the ability to recover rapidly from cold stress. A comprehensive examination of the histological, physiological, biochemical, and molecular responses of P. lagowskii to low temperatures is crucial for developing effective strategies for cultivating this species in challenging environments.

PCSK9 inhibitor effectively alleviated cognitive dysfunction in a type 2 diabetes mellitus rat model.

The incidence of diabetes-associated cognitive dysfunction (DACD) is increasing; however, few clinical intervention measures are available for the prevention and treatment of this disease. Research has shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, particularly SBC-115076, have a protective effect against various neurodegenerative diseases. However, their role in DACD remains unknown. In this study, we aimed to explore the impact of PCSK9 inhibitors on DACD. Male Sprague-Dawley (SD) rats were used to establish an animal model of type 2 diabetes mellitus (T2DM). The rats were randomly divided into three groups: the Control group (Control, healthy rats, n = 8), the Model group (Model, rats with T2DM, n = 8), and the PCSK9 inhibitor-treated group (Treat, T2DM rats treated with PCSK9 inhibitors, n = 8). To assess the spatial learning and memory of the rats in each group, the Morris water maze (MWM) test was conducted. Hematoxylin-eosin staining and Nissl staining procedures were performed to assess the structural characteristics and functional status of the neurons of rats from each group. Transmission electron microscopy was used to examine the morphology and structure of the hippocampal neurons. Determine serum PCSK9 and lipid metabolism indicators in each group of rats. Use qRT-PCR to detect the expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in the hippocampal tissues of each group of rats. Western blot was used to detect the expression of PCSK9 and low-density lipoprotein receptor (LDLR) in the hippocampal tissues of rats. In addition, a 4D label-free quantitative proteomics approach was used to analyse protein expression in rat hippocampal tissues. The expression of selected proteins in hippocampal tissues was verified by parallel reaction monitoring (PRM) and immunohistochemistry (IHC). The results showed that the PCSK9 inhibitor alleviated cognitive dysfunction in T2DM rats. PCSK9 inhibitors can reduce PCSK9, total cholesterol (TC), and low-density lipoprotein (LDL) levels in the serum of T2DM rats. Meanwhile, it was found that PCSK9 inhibitors can reduce the expression of PCSK9, IL-1β, IL-6, and TNF-α in the hippocampal tissues of T2DM rats, while increasing the expression of LDLR. Thirteen potential target proteins for the action of PCSK9 inhibitors on DACD rats were identified. PRM and IHC revealed that PCSK9 inhibitors effectively counteracted the downregulation of transthyretin in DACD rats. This study uncovered the target proteins and specific mechanisms of PCSK9 inhibitors in DACD, providing an experimental basis for the clinical application of PCSK9 inhibitors for the potential treatment of DACD.