Decreased Lipid Levels Research Articles

Strawberry anthocyanin pelargonidin-3-glucoside attenuated OA-induced neurotoxicity by activating UPRmt.

In this study, network pharmacology analysis revealed that strawberry anthocyanins mainly interfered with lipid metabolism and nerve-related signaling pathways. Pelargonidin-3-glucoside (Pg3G), one of the main anthocyanins in strawberry, was screened as the most effective anthocyanin for attenuating excess lipid accumulation. Moreover, Pg3G decreased lipid levels, relieved oxidative stress, and restored abnormal behavioral activities in Caenorhabditis elegans under oleic acid (OA) exposure. Meanwhile, Pg3G increased the expression of HSP-6 and HSP-60 proteins and activated the mitochondrial unfolded protein response (UPRmt), while beneficial effects of Pg3G were impaired in the ubl-5 knockout strain, suggesting that ubl-5 may be a key target for improving OA-induced neurotoxicity. Expressions of neurotransmitter transmission-related genes showed great correlations with genes involved in lipid metabolism and UPRmt, further explaining the underlying mechanism of Pg3G in neuroprotection. Our findings emphasize the key role of UPRmt in alleviating OA-induced neurotoxicity of Pg3G, providing a theoretical basis for the research and development of strawberry anthocyanins as a dietary supplement for lipid reduction and treatment of neurodegenerative diseases.

AlphaFold-Based AI Docking Reveals AMPK/SIRT1-TFEB Pathway Modulation by Traditional Chinese Medicine in Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD) is a chronic, progressive disorder characterized by hepatic steatosis and excessive lipid accumulation. Its high global adult prevalence (approximately 50.7%), however, FDA-approved therapeutic drugs remains lacking. Qigui Jiangzhi Formula (QGJZF) shows promise in treating MAFLD by effectively decreasing lipid levels and improving hepatic steatosis, however its mechanisms remain unclear. This study investigated QGJZF's effects in high-fat diet-induced zebrafish and golden hamsters, and in palmitate (PA) and oleic acid (OA) - induced HepG2 cells, using the SymMap database to identify potential targets and pathways of QGJZF in MAFLD and AlphaFold algorithms to predict protein structures. In vivo, QGJZF significantly alleviatied hepatic lipid deposition. Intriguingly, QGJZF decreased lipid droplets and its levels are negative correlation with the numbers of autolysosomes, indicating that QGJZF's mechanism of meliorating liver lipid deposition may be relate to the regulation of autophagy. QGJZF upregulated the expressions of phosphorylated -Adenosine 5'-monophosphate (AMP) - activated protein kinase (p-AMPK), Sirtuin deacetylase 1 (SIRT1) and Transcription factor EB (TFEB), accompanied by the changes in autophagy-related proteins. In vitro, QGJZF inhibited the lipid deposition in, and its effect was blocked by Baf-A1, which was mediated through upregulation of TFEB and its mediated autophagy-lysosomal pathway. Moreover, cotreatment with AMPK inhibitor Compound C, the regulation of QGJZF on TFEB, SIRT1, autophagy-related protein levels, and lipid deposition were reversed. Network pharmacology identified the PRKAA2 (AMPK) and SIRT1 as key hub targets. Futher analysis of their structures using AlphaFold3 algorithms, yielded high-ranking scores of 0.97 and 0.93, respectively. Liquid chromatography-mass spectrometry combined with molecular docking expounded its five compounds in QGJZF binding to AMPK protein. These findings suggest that QGJZF as a therapeutic agent in augmenting autophagy-facilitated lipid clearance for the management of MAFLD via AMPK/SIRT1-TFEB axis.

Acer tegmeutosum Maxim extract alleviates acute alcohol-induced liver disease and regulates gut microbiota dysbiosis in mice.

Acer tegmentosum Maxim (AT) has a variety of pharmacological activities, however, the effects of AT on liver injury and gut microbiota in alcoholic liver disease (ALD) mice is still unclear. This study aimed to evaluate the preventive effect of AT extract on acute alcoholic liver disease. Six-week-old male C57BL/6J mice were randomly divided into 6 groups. Each group was intragastrically treated saline or different concentration of AT extract solution for 5 weeks continuously. After the last gavage, except for the NC group, all the other groups were gavaged twice with 56% alcohol to establish the acute ALD model and biochemical indexes, histopathological, and gut microbiota were analyzed. Established an acute ALD mouse model and detected serum, liver oxidation levels, and alcohol metabolism-related gene expressions. Through 16S rRNA sequencing, analyzed gut microbiota, explored the relationship between gut microbiota and liver indicators. AT extract significantly decreased lipid levels, promoted ADH, ALDH, and increased the antioxidant activities. Meanwhile, AT extract significantly downregulated the expression of lipid oxidation and inflammatory factors, upregulated alcohol metabolism genes. In addition, 16S rRNA sequencing and analysis showed that AT extract effectively regulated the gut microbiota diversity of ALD mice, significantly improved the structural disturbance of intestinal microflora. AT extract regulated gut microbiota and had a strong correlation with serum, liver-related indexes, and gene expression levels. All these results showed that AT can alleviate alcohol induced liver injury by regulating oxidative stress, inflammatory response, alcohol metabolism, and gut microbiota disorder.

Preparation and Hypoglycemic Effect of Magnolia Officinalis Polysaccharide Oral Liquid.

In this paper, an oral liquid containing Magnolia officinalis polysaccharide was formulated and its hypoglycemic effects were investigated. An orthogonal test was conducted based on single-factor experiments to optimize the formulation guided by sensory evaluations. Its stability and safety were also assessed. The oral liquid was administered via gavage to STZ-induced diabetic mice at low (2.5mL/kg), medium (5mL/kg) and high (10mL/kg) doses. Blood glucose levels were monitored weekly. After 8weeks of treatment, the oral glucose tolerance test (OGTT) was performed and fasting insulin levels, lipid profiles, oxidative stress levels in serum and liver, and the activities of hexokinase (HK) and pyruvate kinase (PK) in the liver were measured. Results indicated that the optimal formulation contained 0.2% steviol glycosides, 0.2% ascorbic acid, a pH of 5.0, and 0.5% ginger juice, yielding a sensory evaluation score of 94 ± 0.58. The oral liquid remained stable at room temperature for 12months and passed acute oral toxicity testing. After 8weeks, diabetic mice exhibited a significant reduction in blood glucose levels (P < 0.01), enhanced glucose metabolism, increased fasting insulin levels, and decreased lipid levels. Additionally, antioxidant capacity improved, and HK and PK activities increased significantly in the diabetic mice. In conclusion, the Magnolia officinalis polysaccharide oral liquid demonstrated potential antidiabetic effects by promoting glucose utilization in peripheral tissues, increasing fasting insulin levels, and enhancing antioxidant capacity alongside HK and PK activities. This formulation could represent a promising hypoglycemic health product.

Hypolipidemic and Hepatoprotective Effect of Linum usitatissimum and Moringa oleifera Seeds in Diabetic Induced Damage in Rats

Background Diabetes mellitus is a chronic metabolic disorder and a fast-growing global problem. Studies have shown that Linum usitatissimum has anti-inflammatory and antioxidant properties that decrease blood sugar and cholesterol levels, and Moringa oleifera possesses hepatoprotective, anti-inflammatory and hypoglycaemic effects. Hence, this study investigated both extracts’ hypolipidemic and hepatoprotective effects on diabetes. Purpose To study the improvement in glucose level, lipid levels (total cholesterol, high-density lipoprotein, low-density lipoprotein) and hepatic parameters after giving L. usitatissimum and M. oleifera seed extract combination in diabetic rats. Methods A total of 36 healthy male Wistar rats were taken and divided into six groups (groups I–VI). Diabetes was induced by administering a single intraperitoneal injection of streptozotocin in overnight fasted rats. The mixture of aqueous extract of L. usitatissimum and M. oleifera seeds was prepared and given to rats of groups IV–VI daily for 4 weeks. After 28 days, the blood sample was collected from all the rats, and biochemical parameters were determined. Results All the values are expressed as mean ± standard deviation (SD). Significant decreases in lipid levels, urea, creatinine and liver function tests were seen at the end of 1 month in all the three groups receiving the extract. Conclusion From our study, it was found that the administration of L. usitatissimum and M. oleifera seeds extract possesses excellent hypolipidemic and hepatoprotective properties, making them effective in preventing long-term complications of diabetes.

Psycho-biological mechanisms involved in suicidal risk, suicide attempts, and aggression: A replication and extension in bipolar disorder.

Despite studies showing the individual roles of childhood maltreatment, alexithymia, impulsivity, and biological markers in suicide and aggression in bipolar disorder (BD), combined influence of these factors has not been studied yet. This study aimed to explore this issue in 353 individuals with BD completing self-report and clinician-rated measures. Blood samples were also taken to evaluate biological markers. Higher C-reactive protein (CRP) and triglycerides (TG) and lower total cholesterol (TC) were observed in alexithymic people. Individuals with childhood maltreatment showed elevated CRP and lower TC and high-density lipoprotein cholesterol (HDLC). Those with both alexithymia and maltreatment displayed the most adverse profile regarding CRP and lipids. Depressive and manic symptoms, suicidal ideation, and low TC and HDL-C were associated with suicide attempts, while age, depressive and manic symptoms, childhood maltreatment, alexithymia, impulsivity, CRP, and low HDL-C accounted for suicidal risk. Aggression was linked to gender, impulsivity, and reduced low-density lipoprotein cholesterol (LDL-C). A cross-sectional design is a limitation of the study. The study underscores the relationships between psychological and altered biomarkers, particularly elevated CRP and decreased lipid levels, and their roles in contributing to suicide and aggression, proposing a psychobiological model in BD.

Analysis of Lipid Metabolism in Adipose Tissue and Liver of Chinese Soft-Shelled Turtle Pelodiscus sinensis During Hibernation.

Hibernation serves as an energy-conserving strategy that enables animals to withstand harsh environments by reducing their metabolic rate significantly. However, the mechanisms underlying energy adaptation in hibernating ectotherms, such as Pelodiscus sinensis, remain contentious. This paper first reports the decrease in lipid levels and the expression of metabolism-related genes in P. sinensis during hibernation. The results of physiological and biochemical analysis showed that adipocyte cell size was reduced and liver lipid droplet (LD) contents were decreased during hibernation in P. sinensis. Concurrently, serum levels of triglycerides (TGs), total cholesterol (TC), non-esterified fatty acids (NEFAs), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) were diminished (n = 8, p < 0.01), while an increase in serum glucose (Glu) (n = 8, p < 0.01) was noted among hibernating P. sinensis. These observations suggest a shift in energy metabolism during hibernation. To gain insights into the molecular mechanisms, we performed integrated transcriptomic and lipidomic analyses of adipose tissue and livers from summer-active versus overwintering P. sinensis, which revealed downregulation of free fatty acids (FFAs), triglycerides (TGs), diglycerides (DGs), and ceramides (Cers) during hibernation. The results of GSEA analysis showed that metabolic pathways associated with lipid metabolism, including glycerolipid metabolism and regulation of lipolysis in adipocytes, were suppressed significantly. Notably, acute cold exposure induced significant downregulation of genes related to lipolysis such as PNPLA2, ABHD5, LPL, CPT1A, and PPARα. The results indicate that lipolysis is suppressed during hibernation in P. sinensis. Collectively, these findings deepen our understanding of survival mechanisms and elucidate the unique energy adaptation strategies employed by hibernating ectotherms. Future research should explore the implications of these findings for the conservation of ectotherms and the applications for artificially inducing hibernation.

A Graphene-Based Lipid Modulation Nanoplatform for Synergetic Lipid Starvation/Chemo/Photothermal Therapy of Oral Squamous Cell Carcinoma.

Chemotherapy is one of the most commonly used treatments for oral squamous cell carcinoma (OSCC), but its use is limited by drug resistance and severe systemic toxicity. To eliminate these side effects and improve anti-tumor efficacy, several therapeutic approaches have been developed for use with chemotherapy. In this study, we developed a graphene-based lipid modulation nanoplatform (NSD) that carries SB-204990, a small molecule inhibitor specific for ATP citrate lyase (ACLY), and doxorubicin (DOX), a chemotherapeutic agent, and the trio enables synergistic treatment of OSCC with lipid starvation, chemotherapy, and photothermal therapy. We first determined whether ACLY expression was upregulated in OSCC, and then assessed the growth inhibitory effects of SB-204990 on SCC-15 cells and changes in lipid (acetyl coenzyme A, free fatty acids, and cholesterol) levels. We characterized NSD and then evaluated the stability, photothermal properties, drug loading, and release ability of NSD. Finally, the therapeutic effects of NSD on OSCC were investigated by in vitro and in vivo experiments, and the changes in lipid levels in OSCC tissues after ACLY inhibition were further evaluated. The results showed that ACLY was highly expressed in OSCC, and ACLY inhibition produced reproductive suppression and decreased lipid levels in SCC-15 cells. The NSD nanoplatform possessed good stability, photothermal properties, high drug loading capacity and controlled release. In addition, the triple therapy achieved satisfactory anticancer effects in both in vivo and in vitro assays, and the inhibition rate of tumors was as high as 99.4% in the NSD+Laser treatment group. The changes in tumor cell lipid levels and cell proliferation arrest induced by ACLY inhibition suggest that ACLY may be a promising target for lipid starvation therapy and resistance to chemoresistance, and its inhibitors are expected to become new anticancer drugs. The NSD nanocarrier system enables synergistic treatment with lipid starvation, chemotherapy, and photothermal therapy, which represents an innovative approach to combating tumors.

A comparative study of hypolipidemic effect of atorvastatin and Coriandrum sativum in triton-induced hyperlipidemic albino rat model

Background: Hyperlipidemia is the main factor responsible for coronary artery disease. Atorvastatin commonly used, as a competitive inhibitor of HMG-Co-A reductase, is known to reduce LDL and triglyceride levels and increase HDL levels. Coriandrum sativum (Coriander) belongs to the Apiaceae family and has hypolipidemic, antidiabetic, and antioxidant properties. Triton WR1339 has been used by several studies to induce hypercholesterolemia in animals which acts on both the synthesis and excretory phase. This study aimed to compare the hypolipidemic effect of Coriandrum sativum and atorvastatin in triton-induced hyperlipidemic rats. Methods: Following approval from the Institutional Animal Ethics committee, 36 Wistar albino rats were divided into 6 groups of 6 animals each. Triton 200mg IP was administered to all the groups except Group 1 (control). Groups 3 and 4 received Coriander extract 300mg/kg and Atorvastatin 80mg/kg orally with Triton. Groups 5 and 6 received Coriander extract and Atorvastatin respectively 22 hours later. Lipid profile was estimated 24 hours before, 24 and 48 hours after administering Triton. Results: In the synthesis phase, there is a statistically significant increase in the lipid levels in Groups 2, 5, and 6 compared to Groups 3 and, 4 indicating hypolipidemic effects of both Coriander extract and Atorvastatin. In the excretory phase, all groups have shown a decrease in lipid levels but a decrease in total cholesterol level in Group 5 compared to Group 3 was significant. Conclusions: Atorvastatin and Coriander extract both affect the lipid levels in the synthesis and excretory phase. Even though coriander cannot replace atorvastatin in the management of hyperlipidemia, it can be used as an adjuvant to atorvastatin to reduce the cost effects and adverse reactions caused by allopathic medicines.

Impact of lipid content on oxygen reactive species and viability predictors in vitrified bovine embryos

Given the significant variation in lipid levels among bovine embryos, our study was designed to associate lipid content to oxidative stress in individual embryos undergoing vitrification, and to assess how this and other morphological parameters impacts cryosurvival. Linear and logistic regression were performed to understand the influence of the variables in the cryosurvival. T-test or Kruskal Wallis were employed to compare means. Vitrified embryos revealed a positive correlation between lipid content and oxidative stress post-warming both 2 h (p = 0.025, n = 64) and 48 h (p < 0.001, n = 122) after warming. Lipid levels explained (p < 0.001) up to 51 % (multiple R-squared) of oxidative stress variability. Compared to fresh embryos, a negative influence (p = 0.01) of vitrification-warming procedures was detected in lipid levels. Vitrified embryos exhibited lower (p < 0.001, n = 90) mean lipid content compared to fresh counterparts 48 h post-warming, and similar (p = 0.24) oxidative stress levels. No impact of lipid content or oxidative stress levels was detected on hatchability or embryo quality 48 h post-warming (n = 99). Expansion just after (0 h) and 2 h after warming resulted in a higher chance of hatching (p = 0.015 and p = 0.008, OR 1.30 and 1.58), and a positive association was observed between expansion at 0 h (p = 0.002) and embryo area (p = 0.047) with cell number. In conclusion, a decrease in lipid levels was found following vitrification-warming procedure and an individual association between lipids and oxidative stress is present in vitrified embryos. Lipids or oxidative stress levels was not linked to survivability of vitrified embryos 48 h following warming. Expansion at 0 h indicates a better chance for hatching and higher cell numbers in vitrified embryos.

Integrated metabolomics and network pharmacology to reveal the mechanisms of Shexiang Baoxin pill against atherosclerosis

BackgroundAtherosclerosis is a disease marked by the development of lipid lesions within the endothelium and continues to be a prominent contributor to global mortality. Shexiang Baoxin pill (SBP) has been employed in the management of numerous cardiovascular diseases, but the complex mechanisms by which it operates remain obscure. This research was conducted to determine the potential impact of SBP on atherosclerosis and the underlying regulatory mechanism involved. MethodNetwork pharmacology was utilized to predict the key drug-disease targets, and a nontargeted metabolomic assay was applied to identify the key metabolites and metabolic pathways. A mouse atherosclerosis model was constructed to clarify the protective effect of SBP on atherosclerosis, and in vivo and in vitro tests were performed to verify the analysis results and clarify the mechanism through which SBP affects atherosclerosis. ResultsThe results show that SBP can exert a protective effect in vivo by decreasing lipid levels, plaque formation and endothelial damage. Network pharmacology and metabolomics revealed that MAPK3, AKT1 and STAT3 were the hub targets and that trimethylamine n-oxide (TMAO) was the pivotal metabolite. Due to the atherogenic effect of TMAO, the corresponding protective effect of SBP was investigated in vitro. SBP inhibited TMAO-induced endothelial cell apoptosis and oxidative stress and counteracted the upregulation of MAPK3, AKT1, and STAT3 expression. Molecular docking and enzymatic inhibition suggested that the active components of SBP could bind stably to key target proteins. ConclusionTaken together, based on the integrated metabolomics and network pharmacology, our findings suggest that SBP may be implicated in TMAO-induced atherosclerosis by affecting endothelial function and bile acid synthesis. We observed that SBP may ameliorate atherosclerosis by regulating TMAO levels through multiple pathways, which may provide a novel direction and insight for SBP involved in cardiovascular protection by mediating the gut-heart axis.

Natural High Strontium Mineral Water Might Reduce Liver Protein Synthesis: A Non-Targeted Metabolomics Study in Rats.

Strontium-rich mineral water (strontium > 0.20mg/L) is the second largest type of mineral water on commercial drinking water market. Exposure to high levels of strontium through drinking water or soil may interfere with calcium metabolism and increase the risk of cardiovascular and skeletal diseases, but no in-depth mechanism has been disclosed to date. Data on liver metabolic alterations in rats resulted from drinking natural high strontium mineral water (strontium 26.06mg/L, SrHW) or tap water (filtered by activated carbon, strontium 0.49mg/L, TW) for 3months were obtained and analyzed with non-targeted metabolomics strategy. Compared with rats drinking TW, those drinking SrHW showed a significant change in 36 liver metabolites. Among them, 33 liver metabolites (including 14 amino acids, 6 carbohydrates, 4 short-chain fatty acids, 4 organic acids, 2 phenylpropanoic acids, 1 fatty acid, 1 peptide, and 1 bile acid) were down-regulated, and 3 (hydroxyphenyllactic acid, propionylcarnitine and S-adenosine homocysteine) were up-regulated. Metabolic pathway analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and alanine, aspartate and glutamate metabolism are most impacted. Furthermore, the serum prealbumin content also significantly decreased in rats drinking SrHW. Therefore, changes in liver metabolites and serum protein levels suggested that high concentration of strontium in water was associated with decreased liver protein synthesis; changes in liver metabolites suggested that high strontium was associated with decreased lipid levels. In conclusion, high strontium in water may exert a negative effect on protein synthesis, and further study on the dose-response relationship is necessary.

The Effect Of Weight Loss With Lifestyle Changes On LDL Cholesterol: Retrospective Cohort Study

Aim: This study aimed to investigate the rate of decrease in lipid levels with effective lifestyle changes (LC) and the minimum body weight loss necessary for effective lipid reduction in obese patients. Method: The study is a retrospective cohort study. The study included 71 patients who were followed up in the obesity clinic, who were diagnosed with hyperlipidemia but did not use any hyperlipidemia treatment. The patients' high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglyceride, body fat ratio and mass, body mass index (BMI), height and weight information were recorded at the first visit and the 6th month. In our study, patients were divided into two groups (based on the weight loss rates in the 6-month follow-up) those who lost less than 10% of their previous weight and those who lost 10% or more weight and their lipid parameters were compared. Results: LDL-C reduction rates of patients classified according to their weight loss rates were found to be statistically significantly (p=0.011) higher in those with 10% or more weight loss than (group 1=18.48%) in those with less than 10% weight loss (group 2=13.04%). Total cholesterol reduction rates were also significantly (p=0.015) higher in the 1st group than in the 2nd group. According to the findings of our study, at least 10% weight loss is required to decrease total cholesterol and LDL-C significantly. Conclusion: Implementation of primary and secondary prevention strategies to reduce the risk of cardiovascular disease is important in the context of primary care. To reach the targeted LDL-C values, the weight monitoring of obese patients should be considered, and the importance of losing at least 10% of weight as one of the first steps should be emphasized.

SiRNA nanoparticle targeting Usp20 lowers lipid levels and ameliorates metabolic syndrome in mice

Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr−/− mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease.

The augment effects of magnesium hydride on the lipid lowering effect of atorvastatin: an in vivo and in vitro investigation.

There is strong evidence connecting increased serum lipid levels to cardiovascular disorders, including atherosclerosis. Statins is prescribed as the primary medication to decrease lipid levels. Recent research has demonstrated that hydrogen possesses anti-inflammatory and antioxidant properties by modulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1α, ultimately leading to the preservation of lipid homeostasis. Magnesium hydride (MgH2) is a prolonged stable hydrogen storage medium, which can be utilized to investigate its synergistic lipid-lowering effect with statins and its detailed molecular mechanism, both in vivo and in vitro. To ascertain the safety and efficacy of MgH2, we executed a comprehensive research of its influence on both physiological and pathological metrics. We noted a substantial diminution in lipid levels when MgH2 was integrated with atorvastatin, as attested by oil red staining. Furthermore, we scrutinized the regulatory effect of MgH2 on cytochrome P450 3A, which is a metabolic enzyme of statins, and discovered that it could be reduced by the MgH2. Concluding from our results, we propose that MgH2 inhibits the expression of cytochrome P450 3A in the liver and exerts an auxiliary lipid-lowering effect by increasing the blood concentration of statins. By augmenting our comprehension of MgH2's role in ameliorating lipid metabolism, we aspire to develop more promising therapies in the future.

Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Reduces Fat Deposition in Obese Mice by Remodeling the Gut Microbiota

A methionine-restricted diet (MRD) has been shown to reduce body fat deposition and improve obesity-associated metabolic disorders, with emerging evidence implicating the gut microbiota in mediating these effects. This study investigated the effects and underlying mechanisms of fecal microbiota transplantation (FMT) from MRD mouse donors on body fat deposition in obese mice. Five-week-old male C57BL/6J mice were continuously fed a high-fat diet (HFD, 0.86% methionine + 24% fat) to induce obesity, and then randomly divided into three groups. These groups received FMT from 23-week-old male C57BL/6J mice donors continuously fed with normal diet (0.86% methionine + 4.2% fat), HFD, or MRD (0.17% methionine + 24% fat) for eight weeks, respectively. Our results indicate that FMT from MRD mouse donors reduced body weight, plasma lipid levels, and percentage fat mass. Moreover, FMT from MRD mouse donors elevated the abundance of short-chain fatty acid (SCFA)-producing bacteria while decreasing pro-inflammatory bacteria levels in cecal contents. In addition, systemic metabolic processes were altered, featuring heightened SCFA production and enhanced energy metabolism. FMT from MRD mouse donors further facilitated fat catabolism, inhibited fat anabolism, and decreased lipid levels and lipid accumulation in liver. Meanwhile, FMT from MRD mouse donors also promoted fat browning, decreased adipocyte volume, and reduced fat deposition in adipose tissues. These findings underscore the potential of FMT from MRD mouse donors to improve the gut microbiota and reduce body fat deposition in obese mice. Importantly, our results elucidate that MRD intervention in obesity is, in part, mediated by regulating intestinal microbial composition.

Dan-shen Yin promotes bile acid metabolism and excretion to prevent atherosclerosis via activating FXR/BSEP signaling pathway

Ethnopharmacological relevanceDan-shen Yin (DSY), a traditional prescription, has been demonstrated to be effective in decreasing hyperlipidemia and preventing atherosclerosis (AS), but its mechanism remains unknown. We hypothesized that DSY activates farnesoid X receptor (FXR) to promote bile acid metabolism and excretion, thereby alleviating AS. Aim of the studyThis study was designed to explore whether DSY reduces liver lipid accumulation and prevents AS by activating FXR and increasing cholesterol metabolism and bile acid excretion. Materials and methodsThe comprehensive chemical characterization of DSY was analyzed by UHPLC-MS/MS. The AS models of ApoE−/− mice and SD rats was established by high-fat diet and high-fat diet combined with intraperitoneal injection of vitamin D3, respectively. The aortic plaque and pathological changes were used to evaluate AS. Lipid levels, H&E staining and oil red O staining were used to evaluate liver lipid accumulation. The cholesterol metabolism and bile acid excretion were evaluated by enzyme-linked immunosorbent assay, UPLC-QQQ/MS. In vitro, the lipid and FXR/bile salt export pump (BSEP) levels were evaluated by oil red O staining, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. ResultsA total of 36 ingredients in DSY were identified by UPLC-MS/MS analysis. In vivo, high-dose DSY significantly inhibited aortic intimal thickening, improved arrangement disorder, tortuosity, and rupture of elastic fibers, decreased lipid levels, and reduced the number of fat vacuoles and lipid droplets in liver tissue in SD rats and ApoE−/− mice. Further studies found that high-dose DSY significantly reduced liver lipid and total bile acids levels, increased liver ursodeoxycholic acid (UDCA) and other non-conjugated bile acids levels, increased fecal total cholesterol (TC) levels, and augmented FXR, BSEP, cholesterol 7-alpha hydroxylase (CYP7A1), ATP binding cassette subfamily G5/G8 (ABCG5/8) expression levels, while decreasing ASBT expression levels. In vitro studies showed that DSY significantly reduced TC and TG levels, as well as lipid droplets, while also increasing the expression of ABCG5/8, FXR, and BSEP in both HepG2 and Nr1h4 knockdown HepG2 cells. ConclusionThis study demonstrated that DSY promotes bile acid metabolism and excretion to prevent AS by activating FXR. For the prevent of AS and drug discovery provided experimental basis.

The expression of the miR-193, miR-122 and miR-155 profiling and evaluation the serum lipid in antimony-susceptible and resistance patients with cutaneous leishmaniasis

Background &amp; objectives: The current investigation was carried out to evaluate the expression of MicroRNAs miR-193, miR-122 and miR-155 and lipid profile in antimony-susceptible and resistance patients with cutaneous leishmaniasis. Methods: Lesion and blood samples were collected from 27 antimony-resistance and 27 antimony-susceptible patients. mRNA was extracted and synthase to the cDNA using commercial kits according to the manufacturers’ guideline. The expression of miR-193, miR-122 and miR-155 were evaluated using Real-Time PCR technique. The serum lipid profiles were measured by enzymatic methods. Results: Our results indicated that the expression of miR-193, miR-122 and miR-155 was significantly higher in antimony-susceptible patients. The results of current study indicated that downregulation of miRNAs is coupled with low serum LDL-C and triglyceride. Interpretation &amp; conclusion: The downregulation of miRNAs and decrease in lipid levels may be one of the mechanisms of the parasite to escape from host immune system.

Per- and Polyfluoroalkyl Substances: Impacts on Morphology, Behavior and Lipid Levels in Zebrafish Embryos.

The presence of per- and polyfluoroalkyl substances (PFASs) in aquatic environments is often persistent and widespread. Understanding the potential adverse effects from this group of chemicals on aquatic communities allows for better hazard characterization. This study examines impacts on zebrafish (Danio rerio) embryo physiology, behavior, and lipid levels from exposure to perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and heptadecafluorooctanesulfonic acid (PFOS). Embryos were exposed to lethal and sublethal levels of each chemical and monitored for alterations in physiological malformations, mortality, lipid levels, and behavior (only PFOA and PFHxS). The predicted 50% lethal concentrations for 120 hpf embryos were 528.6 ppm PFOA, 14.28 ppm PFHxS, and 2.14 ppm PFOS. Spine curvature and the inability of the 120 hpf embryos to maintain a dorsal-up orientation was significantly increased at 10.2 ppm PFHxS and 1.9 ppm PFOS exposure. All measured 120 hpf embryo behaviors were significantly altered starting at the lowest levels tested, 188 ppm PFOA and 6.4 ppm PFHxS. Lipid levels decreased at the highest PFAS levels tested (375 PFOA ppm, 14.4 PFHxS ppm, 2.42 ppm PFOS). In general, the PFAS chemicals, at the levels examined in this study, increased morphological deformities, embryo activity, and startle response time, as well as decreased lipid levels in 120 hpf zebrafish embryos.

A comparative study of efficacy and safety of glimepiride versus gliclazide as an add on to metformin in Type 2 diabetes mellitus at a tertiary care hospital

Background: Type 2 diabetes mellitus (T2DM) is a chronic disorder with progressive pancreatic β-cell dysfunction and insulin resistance. Hyperglycemia associated with uncontrolled T2DM leads to various diabetes-related complications. Although metformin is the most preferred first-line drug, 5–10% of patients per year subsequently fail to achieve target HbA1c levels, subsequently requiring combination therapy. While efficacy and cost favor the use of sulfonylureas, hypoglycemic episodes limit its use. Newer generation sulfonylureas such as glimepiride and gliclazide are presumed to have lower incidence of hypoglycemia. Aims and Objectives: The aim of the study was to assess the efficacy and safety of glimepiride versus gliclazide as an add-on to metformin in T2DM. Materials and Methods: A total of 60 patients with T2DM (HbA1c 7.0–10.0%, on metformin monotherapy) were recruited and randomized into two groups of 30 cases each. Group A received glimepiride 2 mg as add-on to metformin 1500 mg and Group B received gliclazide 80 mg as add-on to metformin 1500 mg. HbA1c, lipid profile, body mass index, and total blood count were assessed at baseline and at the end 12 weeks of treatment. Fasting blood sugar (FBS) and post prandial blood sugar (PPBS) were assessed at the end of 4, 8, and 12 weeks and adverse events were assessed throughout the study period. Results: There was a significant decrease in HbA1c, FBS, and PPBS scores from baseline to the end of 12 weeks in both groups (P &lt; 0.001), but the difference was not statistically significant between the two groups (P &gt; 0.05). A significant decrease in lipid levels was observed in both groups except for high-density lipoprotein, low-density lipoprotein in the metformin + gliclazide group. The treatment was well tolerated in both groups, with the most common adverse events being nausea, diarrhea, and epigastric pain. Conclusion: Glimepiride and gliclazide are both equally effective as an add-on to metformin in improving glycaemic indices and are well tolerated in the management of uncontrolled T2DM.