Serum copper assessment in patients with polycystic ovary syndrome and tubal infertility: A retrospective 5-year study.

The association between serum copper and polycystic ovary syndrome (PCOS) lacks definitive conclusions, and the intricate interactions with in vitro fertilization (IVF) cycle characteristics in infertility remain insufficiently explored. This retrospective study included 560 patients with tubal infertility (no-PCOS) and 266 patients with PCOS undergoing IVF at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to December 2022. Patients' basic characteristics, hormonal and metabolic parameters, essential trace elements, and IVF cycle characteristics were measured and analyzed. The results revealed a significantly elevated serum copper level in the PCOS group compared to the control group [17.27 (15.54, 19.67) vs 15.4 (13.87, 17.35), µmol/L; p < .001]. Spearman correlation analyses revealed a significant positive correlation between serum copper concentration and body mass index (BMI), fasting glucose (FG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the no-PCOS group. Additionally, a notable negative correlation with high-density lipoprotein (HDL) was observed (r = -.184, p < .001). Within the PCOS group, serum copper concentration correlated significantly with BMI (r = .198, p = .004) and TG (r = .214, p = .002). The linear trend analysis indicated no significant relationship between serum copper concentration and ovarian response as well as preimplantation outcomes in both groups after adjusting for confounding factors. Our study provided evidence of elevated serum copper concentration in PCOS patients, closely associated with lipid metabolism but showing no correlation with IVF outcomes. These findings provide valuable real-world data, enriching our nuanced understanding of the role of copper in female fertility.

Naringin Prevents Diabetic-Induced Dysmetabolism in Male Wistar Rats by Modulating GSK-3 Activities and Oxidative Stress-Dependent Pathways.

Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and glucose dysmetabolism, is a major metabolic disorder accompanied with health and financial burden. Recently, research findings showed that orange peel extract (OPE) has health benefits such as improved insulin sensitivity and glucose metabolism. The present study aimed at establishing the role of naringin from OPE on T2DM-induced glucose and lipid dysmetabolism. Thirty male (30) Wistar rats were randomized into five groups: control, diabetes, diabetes + naringin, diabetes + orange peel, and diabetes + metformin. Oral administration was once per day for 28 days. After 28 days of treatment, naringin ameliorated the diabetes-induced increase in blood sugar, homeostatic model assessment (HOMA) IR, triglyceride, total cholesterol, triglyceride/high density lipoprotein, total cholesterol/high density lipoprotein, triglyceride glucose index, glucose synthase kinase-3, lactate, lactate dehydrogenase, malondialdehyde, c-reactive protein, and tumor necrosis factor α compared with the diabetic untreated animals. Furthermore, naringin reversed diabetes-induced decrease in serum insulin, HOMA B, HOMA S, quantitative insulin-sensitivity check index, high-density lipoprotein, total antioxidant capacity, superoxide dismutase, catalase, glucose transporter-4, and hepatic glycogen. This study showed that naringin prevented diabetes-induced dysglycemia and dyslipidemia via glucose synthase kinase-3 and oxidative stress-dependent pathways.

Formosanin C inhibits pulmonary metastasis by targeting stearyl CoA desaturase-1.

BACKGROUND: Cisplatin (DDP) as the first-line drug has been used in cancer therapy. However, side effects and drug resistance are the challenges of DDP. Disordered lipid metabolism is related to DDP resistance. STUDY DESIGN: In this study, formosanin C (FC) as the main compound of Rhizoma Paridis saponins (RPS) inhibits pulmonary metastasis by targeting stearyl CoA desaturase-1. METHODS AND RESULTS: RPS prolonged the survival period of mice, reduced pulmonary metastases and alleviated colon toxicity caused by DDP. FC as the main compound of RPS enhanced the anti-tumor and anti-metastatic effects of DDP. FC decreased the mRNA level of SCD1 and the content of lipid droplets (LDs) in lung cancer cells. Molecular dynamics and isothermal titration calorimetry verified the binding stability and spontaneously between FC and SCD1. SiSCD1 reduced the content of LDs in cell lines and increased mitochondria (mtROS), which was consistent with the results of FC treatment. The combination group decreased DNA repair associated protein as well as DDP resistance markers such as ERCC1 and 53bp1, and increased DNA damage marker like γH2AX, which indirectly confirmed the occurrence of mtROS. In addition, FC combination with DDP also affected epithelial-mesenchymal transition-related protein like VIM and CDH1 in vivo experiments, and thereby inhibited pulmonary metastasis. CONCLUSION: Our research indicated that the FC as the main compound of RPS targeted the CY2 domain of SCD1, inhibited lipid metabolism in mice, and thereby suppressed cancer metastases. This provided support for use of FC to treat cancer based on lipid metabolism pathway.

Cholestenoic acid as endogenous epigenetic regulator decreases hepatocyte lipid accumulation in vitro and in vivo.

Cholestenoic acid (CA) has been reported as an important biomarker of many severe diseases, but its physiological and pathological roles remain unclear. This study aimed to investigate the potential role of CA in hepatic lipid homeostasis. Enzyme kinetic studies revealed that CA specifically activates DNA methyltransferases 1 (DNMT1) at low concentration with EC50 = 1.99 × 10-6 M and inhibits the activity at higher concentration with IC50 = 9.13 × 10-6 M, and specifically inhibits DNMT3a, and DNMT3b activities with IC50= 8.41 × 10-6 M and IC50= 4.89 × 10-6 M, respectively. In a human hepatocyte in vitro model of high glucose (HG)-induced lipid accumulation, CA significantly increased demethylation of 5mCpG in the promoter regions of over 7,000 genes, particularly those involved in master signaling pathways such as calcium-AMPK and 0.0027 at 6 h. RNA sequencing analysis showed that the downregulated genes are affected by CA encoding key enzymes, such as PCSK9, MVK, and HMGCR, which are involved in cholesterol metabolism and steroid biosynthesis pathways. In addition, untargeted lipidomic analysis showed that CA significantly reduced neutral lipid levels by 60% in the cells cultured in high-glucose media. Administration of CA in mouse metabolic dysfunction-associated steatotic liver disease (MASLD) models significantly decreases lipid accumulation, suppresses the gene expression involved in lipid biosynthesis in liver tissues, and alleviates liver function. This study shows that CA as an endogenous epigenetic regulator decreases lipid accumulation via epigenetic regulation. The results indicate that CA can be considered a potential therapeutic target for the treatment of metabolic disorders.NEW & NOTEWORTHY To our knowledge, this study is the first to identify the mitochondrial monohydroxy bile acid cholestenoic acid (CA) as an endogenous epigenetic regulator that regulates lipid metabolism through epigenome modification in human hepatocytes. The methods used in this study are all big data analysis, and the results of each part show the global regulation of CA on human hepatocytes rather than narrow point effects.

The metabolism of membrane lipid participates in the occurrence of chilling injury in cold-stored banana fruit.

Banana fruit is highly vulnerable to chilling injury (CI) during cold storage, which results in quality deterioration and commodity reduction. The purpose of this study was to investigate the membrane lipid metabolism mechanism underlying low temperature-induced CI in banana fruit. Chilling temperature significantly induced CI symptoms in banana fruit, compared to control temperature (22 °C). Using physiological experiments and transcriptomic analyses, we found that chilling temperature (7 °C) increased CI index, malondialdehyde content, and cell membrane permeability. Additionally, chilling temperature upregulated the genes encoding membrane lipid-degrading enzymes, such as lipoxygenase (LOX), phospholipase D (PLD), phospholipase C (PLC), phospholipase A (PLA), and lipase, but downregulated the genes encoding fatty acid desaturase (FAD). Moreover, chilling temperature raised the activities of LOX, PLD, PLC, PLA, and lipase, inhibited FAD activity, lowered contents of unsaturated fatty acids (USFAs) (γ-linolenic acid and linoleic acid), phosphatidylcholine, and phosphatidylinositol, but retained higher contents of saturated fatty acids (SFAs) (stearic acid and palmitic acid), free fatty acids, phosphatidic acid, lysophosphatidic acid, diacylglycerol, a lower USFAs index, and a lower ratio of USFAs to SFAs. Together, these results revealed that chilling temperature-induced chilling injury of bananas were caused by membrane integrity damage and were associated with the enzymatic and genetic manipulation of membrane lipid metabolism. These activities promoted the degradation of membrane phospholipids and USFAs in fresh bananas during cold storage.

Functional role of skeletal muscle-derived interleukin-6 and its effects on lipid metabolism.

The detrimental impact of obesity on human health is increasingly evident with the rise in obesity-related diseases. Skeletal muscle, the crucial organ responsible for energy balance metabolism, plays a significant role as a secretory organ by releasing various myokines. Among these myokines, interleukin 6 (IL-6) is closely associated with skeletal muscle contraction. IL-6 triggers the process of lipolysis by mobilizing energy-storing adipose tissue, thereby providing energy for physical exercise. This phenomenon also elucidates the health benefits of regular exercise. However, skeletal muscle and adipose tissue maintain a constant interaction, both directly and indirectly. Direct interaction occurs through the accumulation of excess fat within skeletal muscle, known as ectopic fat deposition. Indirect interaction takes place when adipose tissue is mobilized to supply the energy for skeletal muscle during exercise. Consequently, maintaining a functional balance between skeletal muscle and adipose tissue becomes paramount in regulating energy metabolism and promoting overall health. IL-6, as a representative cytokine, participates in various inflammatory responses, including non-classical inflammatory responses such as adipogenesis. Skeletal muscle influences adipogenesis through paracrine mechanisms, primarily by secreting IL-6. In this research paper, we aim to review the role of skeletal muscle-derived IL-6 in lipid metabolism and other physiological activities, such as insulin resistance and glucose tolerance. By doing so, we provide valuable insights into the regulatory function of skeletal muscle-derived myokines in lipid metabolism.

Azadirachtin exposure inhibit ovary development of Spodoptera litura (Lepidoptera: Noctuidae) by altering lipids metabolism event and inhibiting insulin signaling pathways.

Lipids are main energy source for insects reproduction, which are becoming emerging target for pest management. Azadirachtin (AZA) is a multi-targeted and promising botanical insecticide, but its reproduction toxicity mechanism related to lipids metabolism is poorly understood. Here, we applied lipidomic and transcriptomic to provide a comprehensive resource for describing the effect of AZA on lipids remodeling in ovary of Spodoptera litura. The results showed that AZA exposure obviously altered the contents of 130 lipids subclasses (76 upregulated and 54 downregulated). In detail, AZA exposure changed the length and saturation degrees of fatty acyl chain of most glycerolipid, phospholipid and sphingolipid as well as the expression of genes related to biosynthesis of unsaturated fatty acids and fatty acids elongation. Besides, following the abnormal lipids metabolism, western blot analysis suggested that AZA induce insulin resistance-like phenotypes by inhibiting insulin receptor substrates (IRS) /PI3K/AKT pathway, which might be responsible for the ovary abnormalities of S. litura. Collectively, our study provided insights into the lipids metabolism event in S. litura underlying AZA exposure, these key metabolites and genes identified in this study would also provide important reference for pest control in future.

Comprehensive analyses of membrane lipids and phenolics metabolisms reveal the developments of chilling injury and browning in Chinese olives during cold storage.

The impacts of chilling injury (CI) temperature (2 °C) and non-CI temperature (8 °C) on the CI development, browning occurrence, and its underlying mechanism in Chinese olives were investigated. The results showed that, 2 °C induced higher levels of CI index, browning degree, chromaticity a* and b* values, but lower values of h°, chlorophyll and carotenoid contents in Chinese olives as compared to 8 °C. Furthermore, 2 °C raised cell membrane permeability, increased the activities of phospholipase D, lipase and lipoxygenase, accelerated the hydrolyses of phosphatidylcholine and phosphatidylinositol to phosphatidic acid, and promoted the conversions of unsaturated fatty acids to saturated fatty acids in Chinese olives. Moreover, 2 °C-stored Chinese olives showed higher activities of peroxidase and polyphenol oxidase, but lower contents of tanin, flavonoid and phenolics. These findings demonstrated that the CI and browning developments in Chinese olives were closely associated with the metabolisms of membrane lipid and phenolics.

Effects of neutral polysaccharide from Platycodon grandiflorum on high-fat diet-induced obesity via the regulation of gut microbiota and metabolites.

The obesity epidemic has become a global problem with far-reaching health and economic impact. Despite the numerous therapeutic efficacies of Platycodon grandiflorum, its role in modulating obesity-related metabolic disorders has not been clarified. In this study, a purified neutral polysaccharide, PGNP, was obtained from Platycodon grandiflorum. Based on methylation and NMR analyses, PGNP was found to be composed of 2,1-ß-D-Fruf residues ending with a (1→2)-bonded α-D-Glcp. The protective effects of PGNP on high-fat HFD-induced obesity were assessed. According to our results, PGNP effectively alleviated the signs of metabolic syndrome, as demonstrated by reductions in body weight, hepatic steatosis, lipid profile, inflammatory response, and insulin resistance in obese mice. Under PGNP treatment, intestinal histomorphology and the tight junction protein, ZO-1, were well maintained. To elucidate the underlying mechanism, 16S rRNA gene sequencing and LC-MS were employed to assess the positive influence of PGNP on the gut microbiota and metabolites. PGNP effectively increased species diversity of gut microbiota and reversed the HFD-induced imbalance in the gut microbiota by decreasing the Firmicutes to Bacteroidetes ratio. The abundance of Bacteroides and Blautia were increased after PGNP treatment, while the relative abundance of Rikenella, Helicobacter were reduced. Furthermore, PGNP notably influenced the levels of microbial metabolites, including the increased levels of cholic and gamma-linolenic acid. Overall, PGNP might be a potential supplement for the regulation of gut microbiota and metabolites, further affecting obesity.

MXene-based wireless facemask enabled wearable breath acetone detection for lipid metabolic monitoring.

Breath acetone (BrAC) detection presents a promising scheme for noninvasive monitoring of metabolic health due to its close correlation to diets and exercise-regulated lipolysis. Herein, we report a Ti3C2Tx MXene-based wireless facemask for on-body BrAC detection and real-time tracking of lipid metabolism, where Ti3C2Tx MXene serves as a versatile nanoplatform for not only acetone detection but also breath interference filtration. The incorporation of in situ grown TiO2 and short peptides with Ti3C2Tx MXene further improves the acetone sensitivity and selectivity, while TiO2-MXene interfaces facilitate light-assisted response calibration. To further realize wearable breath monitoring, a miniaturized flexible detection tag has been integrated with a commercially available facemask, which enables facile BrAC detection and wireless data transmission. Through the hierarchically designed filtration-detection-calibration-transmission system, we realize BrAC detection down to 0.31 ppm (part per million) in breath. On-body breath tests validate the facemask in dynamically monitoring of lipid metabolism, which could guide dieter, athletes, and fitness enthusiasts to arrange diets and exercise activities. The proposed wearable platform opens up new possibility toward the practice of breath analysis as well as daily lipid metabolic management.

Effect of ammonia stress on AMPK regulating-carbohydrate and lipid metabolism in Chinese striped-neck turtle (Mauremys sinensis).

In aquatic organisms, ammonia is one of the major factors that affect energy levels when it exceeds its optimal concentration. Numerous studies have examined the effects of ammonia on aquatic animals, but its effect on metabolism is still unknown. The effect of ammonia on carbohydrates and lipid metabolism in the Chinese striped neck turtle (Mauremys sinensis) was investigated in this study by exposing the turtle to two different ammonia concentrations (A100: 1.53 mg L-1) and (A200: 2.98 mg L-1) for 24 and 48 h, respectively. Our results showed that the mRNA expression of adenosine monophosphate-activated protein kinase α1 (AMPKα1) significantly increased only in A100 at 24 h, whereas its activity increased in both ammonia-exposed groups. The two AMPK-regulated transcription factors responsible for carbohydrate metabolism also exhibited changes in ammonia-treated groups, as hepatocyte nuclear factor-4-alpha (HNF4α) increased and forkhead box protein O1 (FoxO1) decreased. The expression of phosphofructokinase (PFK) and glucose-6-phosphatase (G-6-PAS) was subsequently downregulated. In addition, transcription factors, carbohydrate-responsive element-binding protein (ChREBP), and sterol regulatory element-binding protein 1c (SREBP-1c), which are known to be involved in lipogenesis, were suppressed. These downstream genes include fatty acid synthase, stearoyl CoA desaturase, and acetyl-CoA carboxylase (FAS, SCD-1 and ACC). Moreover, the glucose content decreased, whereas the triglyceride content increased significantly in A200 at 24 h. We concluded that AMPK signaling inhibits gluconeogenesis and lipogenesis, and promotes glycolysis to meet energy demand under stressful conditions in M. sinensis.

Intestinal Ecology Changes in Diarrheic Père David's Deer Revealed by Gut Microbiota and Fecal Metabolites Analysis.

Diarrhea is one of the most common diseases affecting the health of Père David's deer (Elaphurus davidianus). It is believed that an imbalanced intestinal ecology contributes to the etiology of the condition. However, little is known about how the intestinal ecology changes in these diarrheic animals. In this study, 16S rRNA gene sequencing and ultra-high performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) were used to investigate the gut microbiota and fecal metabolites in five Père David's deer with diarrhea. The results showed that when compared with healthy individuals, considerable changes in the gut microbiome were observed in diarrheic animals, including a significant reduction in microbial diversity and gut microbiota composition alterations. Furthermore, the profiles of numerous fecal metabolites were altered in diarrheic individuals, showing large-scale metabolite dysregulation. Among metabolites, acylcarnitines, lysophosphatidylcholine, bile acids, and oxidized lipids were elevated significantly. Constantly, several metabolic pathways were significantly altered. Interestingly, predicted metabolic pathways based on 16S rRNA gene sequence and differential metabolite analysis showed that lipid metabolism, cofactor, and vitamin metabolism were altered in sick animals, indicating microbiota-host crosstalk in these deer. When combined, the results provide the first comprehensive description of an intestinal microbiome and metabolic imbalance in diarrheic Père David's deer, which advances our understanding and potential future treatment of diarrheic animals.

Metabolome analysis shows that ultrasound enhances the lethality of chlorine dioxide against Salmonella Typhimurium by disrupting its material and energy metabolism.

The physiological status of Salmonella after its ultrasonication was investigated to reveal the potential mechanism through which ultrasound enhances the lethality of chlorine dioxide against Salmonella. Applying either the probe ultrasound (US) or water bath ultrasound (WUS) disrupted the cellular structure of Salmonella bacteria, increased the permeability of their bacterial outer membrane (US: 9.00 %, WUS: 11.96 %), and caused intracellular reactive oxygen species to accumulate (US: 13.95 %, WUS: 4.34 %,), which resulted in a reduction of ATP (US: 15.22 %, WUS: 14.15 %) and ATPase activity (US: 3.13 %, WUS: 26.06 %). This series of adverse effects eventually led to the disruption of the metabolic process in Salmonella cells, by mainly altering the metabolism of lipids, small molecules, and energy. Therefore, ultrasound enhances the lethality of chlorine dioxide primarily by disrupting the cellular structure, intracellular material, and energy homeostasis of Salmonella. This finding will promote the development and application of ultrasonic-assisted sterilization technology in food industries.

Pathogenicity and virulence of Mycobacterium leprae.

Leprosy is caused by Mycobacterium leprae (M. leprae) and M. lepromatosis, an obligate intracellular organism, and over 200,000 new cases occur every year. M. leprae parasitizes histiocytes (skin macrophages) and Schwann cells in the peripheral nerves. Although leprosy can be treated by multidrug therapy, some patients relapse or have a prolonged clinical course and/or experience leprosy reaction. These varying outcomes depend on host factors such as immune responses against bacterial components that determine a range of symptoms. To understand these host responses, knowledge of the mechanisms by which M. leprae parasitizes host cells is important. This article describes the characteristics of leprosy through bacteriology, genetics, epidemiology, immunology, animal models, routes of infection, and clinical findings. It also discusses recent diagnostic methods, treatment, and measures according to the World Health Organization (WHO), including prevention. Recently, the antibacterial activities of anti-hyperlipidaemia agents against other pathogens, such as M. tuberculosis and Staphylococcus aureus have been investigated. Our laboratory has been focused on the metabolism of lipids which constitute the cell wall of M. leprae. Our findings may be useful for the development of future treatments.

Zinc normalizes hepatic lipid handling via modulation of ADA/XO/UA pathway and caspase 3 signaling in highly active antiretroviral therapy-treated Wistar rats.

BACKGROUND: Although highly active antiretroviral therapy (HAART) is effective in the management of HIV, it has been reported to induce hepatic injury and non-alcoholic fatty liver (NAFLD). However, there is a lack of data on the roles of the adenosine deaminase (ADA)/xanthine oxidase (XO)/uric acid (UA) pathway and caspase 3 signaling in HAART-induced NAFLD. Also, whether or not zinc confers protection against HAART-induced NAFLD is not known. AIM: This study evaluated the involvement of the ADA/XO/UA pathway and caspase 3 signaling in HAART-induced hepatic lipid accumulation. It also evaluated the possible protective effect of zinc in HAART-induced hepatic lipid accumulation and injury. METHODS: Thirty two male Wistar rats (n = 8/group) were assigned into four groups namely; vehicle-treated (p.o), zinc-treated (3 mg/kg/day of elemental zinc; p.o), HAART-treated (a cocktail of 52.9 mg/kg of Efavirenz, 26.48 mg/kg of Lamivudine, and 26.48 mg/kg of Tenofovir; p.o), and HAART + zinc-treated groups. The treatment lasted for 8 weeks. RESULTS: HAART administration led to increased body weight and hepatic weight, but unaltered hepatic organo-somatic index. HAART exposure also resulted in impaired glucose homeostasis, evidenced by increased fasting blood glucose, hyperinsulinemia, and insulin resistance (IR), increased plasma and hepatic cholesterol and triglycerides, and impaired hepatic function as depicted by elevated hepatic injury markers and reduced glycogen synthase activity and glycogen content. These findings were accompanied by increased plasma and hepatic ADA and XO activities, UA and malondialdehyde levels, inflammatory markers, and caspase 3 activities. However, HAART suppressed plasma and hepatic antioxidant defenses. Furthermore, HAART distorted hepatic histoarchitecture and reduced hepatic sinusoidal diameter. Co-administration of zinc with HAART normalized HAART-induced alterations. CONCLUSIONS: These findings showed that downregulation of the ADA/XO/UA pathway and caspase 3 signalings may rescue the liver from HAART-induced lipid accumulation and injury.

Adipokine Retinol Binding Protein 4 and Cardiovascular Diseases.

The morbidity and mortality of cardiovascular diseases (CVDs) have been increasing year by year all over the world and expanding greatly to the younger population, which becomes the leading causes of death globally that threatens human life safety. Prediction of the occurrence of diseases by using risk related adverse events is crucial for screening and early detection of CVDs. Thus, the discovery of new biomarkers that related to risks of CVDs are of urgent in the field. Retinol-binding protein 4 (RBP4) is a 21-kDa adipokine, mainly secreted by adipocytes. Besides its well-established function in the induction of insulin resistance, it has also been found in recent years to be closely associated with CVDs and other risk factors, such as hypertension, coronary heart disease, heart failure, obesity, and hyperlipidemia. In this review, we mainly focus on the progress of research that establishes the correlation between RBP4 and CVDs and the corresponding major risk factors in recent years.

Amelioration of lipid accumulations and metabolism disorders in differentiation and development of 3T3-L1 adipocytes through mulberry leaf water extract.

BACKGROUND: Obesity is a worldwide problem that resulted from the excessive fat accumulation in adipose tissue, leading to the impairment of individual health. Mulberry leaf is an important traditional Chinese medicine and has been used to alleviate obesity for a long term. However, its underlying molecular mechanisms have not been fully elucidated yet. PURPOSE: In this study, we aimed to investigate the inhibition effects of mulberry leaf water extract (MLWE) on lipid accumulation during the process of differentiation of 3T3-L1 preadipocytes and development of mature adipocytes through the combination of molecular biology assays and metabolomic analysis. METHODS: The quality consistency and main chemical ingredients of MLWE were analyzed by high performance liquid chromatography and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), respectively. Oil red O staining was used to mirror lipid accumulation. Lipogenesis-, lipolysis- and inflammation-related genes were evaluated by real-time PCR and western blot, respectively. Untargeted metabolomics were performed by LC-MS/MS. RESULTS: Prepared method and quality of MLWE were stable and reliable. A total of 34 compounds were identified and 14 of them were undoubtedly confirmed. MLWE supplementation could dose-dependently inhibit the aggregation of lipid droplets, and the expressions of sterol regulatory element-binding protein (SREBP)-1c, peroxisome proliferator-activated receptor (PPAR) γ, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increase the expressions of adenosine monophosphate-activated protein kinase (AMPK), hormone-sensitive lipase (HSL) and IL-10 in the differentiation of preadipocytes. Furthermore, MLWE treatment could dose-dependently decrease the level of triglycerides and the expressions of ACC, FAS, TNF-α, and IL-6, and up-regulate the level of glycerol and the expressions of PPARα, adiponectin (ADPN), adiponectin receptor (AdipoR) 1, AdipoR2, AMPK, HSL, and IL-10 in the development of mature adipocytes. Untargeted metabolomics showed that a total of 5 and 18 differential metabolites were reversed by MLWE intervention in the differentiation of preadipocytes and the development of mature adipocytes, respectively, which involved in the biosynthesis of unsaturated fatty acids, arachidonic acid metabolism and glycerophospholipids metabolism. CONCLUSION: Taken together, this study firstly verified that MLWE could effectively alleviate lipid accumulation and inflammation by regulating ADPN/AMPK-mediated signaling pathways and relevant metabolic disturbances including biosynthesis of unsaturated fatty acids, arachidonic acid metabolism and glycerophospholipids metabolism.

Evaluating the reparative effects and the mechanism of action of docosahexaenoic acid on azithromycin-induced lipid metabolism dysfunction.

To explore the reparative effects of DHA on the gut microbiome disturbance and dysfunctional lipid metabolism caused by long-term antibiotic therapy, it was tested on an azithromycin (AZI) mouse antibiotic model. Thirty specific-pathogen-free BALB/c mice (SPF grade, half male and half female) were randomly separated into three groups (n = 10, 5 male and 5 female): control group (CK), azithromycin natural recovery group (AZI) and DHA group (DHA). High-throughput sequencing and bioinformatics methods were used to analyze the gut microbiome. ELASE kits were used to measure blood lipid, lipids in the liver, and bile salt hydrolase (BSH) levels in feces. Gas chromatography and UPLC-MS/MS were employed to detect DHA and bile acids contents in liver, respectively. Real-time polymerase chain reaction (RT-PCR) was used to measure the expression of key enzymes involved in lipid metabolism. Long-term AZI treatment led to dyslipidemia, gut microbiome disturbance and anxious behaviors in the mouse model. DHA was found to significantly improve the dyslipidemia and anxiety-like behaviors induced by AZI. DHA had no effect on the structure of gut microbiome and bile acids contents but increased the content of the metabolic enzyme BSH in gut microbiota and normalized the expression of enzymes involved in lipid metabolism.

Protective effect of quercetin against the metabolic dysfunction of glucose and lipids and its associated learning and memory impairments in NAFLD rats.

BACKGROUND: Quercetin (QUE) is a flavonol reported with anti-inflammatory and antioxidant activities, and previous results from the group of this study have demonstrated its neuroprotective effect against lipopolysaccharide-induced neuropsychiatric injuries. However, little is known about its potential effect on neuropsychiatric injuries induced or accompanied by metabolic dysfunction of glucose and lipids. METHODS: A nonalcoholic fatty liver disease (NAFLD) rat model was induced via a high-fat diet (HFD), and glucolipid parameters and liver function were measured. Behavioral performance was observed via the open field test (OFT) and the Morris water maze (MWM). The plasma levels of triggering receptor expressed on myeloid cells-1 (TREM1) and TREM2 were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of Synapsin-1 (Syn-1), Synaptatogmin-1 (Syt-1), TREM1 and TREM2 in the hippocampus were detected using western blotting. Morphological changes in the liver and hippocampus were detected by HE and Oil red or silver staining. RESULTS: Compared with the control rats, HFD-induced NAFLD model rats presented significant metabolic dysfunction, hepatocyte steatosis, and impaired learning and memory ability, as indicated by the increased plasma concentrations of total cholesterol (TC) and triglyceride (TG), the impaired glucose tolerance, the accumulated fat droplets and balloon-like changes in the liver, and the increased escaping latency but decreased duration in the target quadrant in the Morris water maze. All these changes were reversed in QUE-treated rats. Moreover, apart from improving the morphological injuries in the hippocampus, treatment with QUE could increase the decreased plasma concentration and hippocampal protein expression of TREM1 in NAFLD rats and increase the decreased expression of Syn-1 and Syt-1 in the hippocampus. CONCLUSIONS: These results suggested the therapeutic potential of QUE against NAFLD-associated impairment of learning and memory, and the mechanism might involve regulating the metabolic dysfunction of glucose and lipids and balancing the protein expression of synaptic plasticity markers and TREM1/2 in the hippocampus.

Concentration of LDLR, degree of hepatic fibrosis and hepatic steatosis in patients with chronic hepatitis B infection treated with tenofovir disoproxil fumarate.

INTRODUCTION: Epidemiological data indicate that one-third of the world's population have serological markers of hepatitis B virus infection. Hepatic steatosis is often observed in patients with chronic liver diseases. The exact mechanisms of hepatic steatosis progression and the efficacy of antiviral therapy in patients with CHB and hepatic steatosis are not yet fully understood. OBJECTIVE: The aim of the study was to investigate the LDLR concentration and degree of hepatic fibrosis and hepatic steatosis in patients with chronic hepatitis B infection during tenofovir disoproxil fumarate therapy. MATERIAL AND METHODS: The study group consisted of 54 patients with CHB. The LDLR concentration, assessment of the degree of hepatic fibrosis, hepatic steatosis, total cholesterol, low density lipoprotein, high density lipoprotein and triglyceride concentrations, were assessed at the beginning of therapy, 6 months later, and 12 months after commencement of therapy. The control group consisted of 18 healthy individuals. RESULTS: The mean LDLR concentration in the studied groups was statistically significantly lower (p<0.05) than in the controls. The antiviral therapy based on TDF had no influence on the LDLR concentration and HBsAg level. CONCLUSIONS: The results indicate a statistically significant lower(p<0.05) concentration of LDLR in patients with chronic hepatitis B infection. Negative correlations between HBsAg level and LDLR concentration in patients with chronic HBV, at all stages of the study may indicate, that HBsAg protects hepatocytes from LDL accumulation.