Alleviation of Lipid Disorder and Liver Damage in High-Fat Diet-Induced Obese Mice by Selenium-Enriched Cardamine violifolia with Cadmium Accumulation.

BACKGROUND/OBJECTIVES: As a hyperaccumulator of selenium (Se), Cardamine violifolia (Cv) and its peptide extract could ameliorate the negative effects of a high-fat diet (HFD). However, the effects of the coaccumulation of cadmium (Cd) in Se-enriched Cv (Cv2) and the potential confounding effect on the roles of enriched Se remain unknown. We aimed to investigate whether Cv2 could alleviate HFD-induced lipid disorder and liver damage. METHODS: Three groups of 31-week-old female mice were fed for 41 weeks (n = 10-12) with a control Cv-supplemented diet (Cv1D, 0.15 mg Se/kg, 30 µg Cd/kg, and 10% fat calories), a control Cv-supplemented HFD (Cv1HFD, 45% fat calories), and a Cv2-supplemented HFD (Cv2HFD, 1.5 mg Se/kg, 0.29 mg Cd/kg, and 45% fat calories). Liver and serum were collected to determine the element concentrations, markers of liver injury and lipid disorder, and mRNA and/or protein expression of lipid metabolism factors, heavy metal detoxification factors, and selenoproteins. RESULTS: Both Cv1HFD and Cv2HFD induced obesity, and Cv2HFD downregulated Selenoi and upregulated Dio3 compared with Cv1D. When comparing Cv2HFD against Cv1HFD, Cv2 increased the liver Se and Cd, the protein abundance of Selenoh, and the mRNA abundance of 10 selenoproteins; reduced the serum TG, TC, and AST; reduced the liver TG, lipid droplets, malondialdehyde, and mRNA abundance of Mtf1 and Mt2; and differentially regulated the mRNA levels of lipid metabolism factors. CONCLUSIONS: Cv2 alleviated HFD-induced lipid dysregulation and liver damage, which was probably associated with its unique Se speciation. However, further research is needed to explore the interaction of plant-coenriched Se and Cd and its effects on health.

Therapeutic potential of palmitoleic acid in non-alcoholic fatty liver disease: Targeting ferroptosis and lipid metabolism disorders.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a metabolic syndrome associated with obesity and type 2 diabetes mellitus. Currently, there are no effective drugs to treat NAFLD. Palmitoleic acid (PA) has demonstrated therapeutic potential in managing various metabolic diseases and inflammation. Although ferroptosis is known to play a critical role in the NAFLD development, it remains unclear whether PA can alleviate NAFLD by inhibiting ferroptosis. METHODS: Thirty C57BL/6 mice were divided into three groups: standard diet, high-fat diet (HFD), and HFD with PA. The experiment lasted 16 weeks. RESULTS: PA alleviated liver injury, hepatitis, and dyslipidemia in HFD-induced NAFLD mice. It improved insulin resistance, downregulated genes and proteins related to fat synthesis, and upregulated genes and proteins linked to lipolysis and fat oxidation. Mechanistically, bioinformatics enrichment revealed the involvement of ferroptosis in NAFLD. PA mitigated oxidative stress and reduced liver iron content in NAFLD. It downregulated acyl-CoA synthetase long-chain family member 4 (ACSL4) expression while upregulating glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression, thereby inhibiting ferroptosis. CONCLUSION: PA exerts a protective effect against liver lipotoxicity by inhibiting lipid metabolism-mediated ferroptosis. These findings provide new insights into preventive and therapeutic strategies for the pathological processes of NAFLD.

Levothyroxine sodium tablets reversed Hashimoto thyroiditis-induced kidney injury, muscle injury, and lipid metabolism disorder: A case report and literature review.

RATIONALE: Hashimoto thyroiditis (HT), a common cause of hypothyroidism, has shown an increasing incidence in recent years, particularly among women. In addition to the common complications such as lipid metabolism disorders, patients with HT may also experience some serious complications, acute kidney injury and severe muscle damage for instance. This article explored the effectiveness of levothyroxine sodium tablets (L-T4) replacement therapy in severe complications of hypothyroidism, including treatment dosage, duration of complication recovery, and whether additional treatment is needed. PATIENT CONCERNS, DIAGNOSES, AND INTERVENTIONS: We described a case of a 52-year-old woman with HT who exhibited kidney injury, muscle injury, and lipid metabolism disorders. The increased levels of serum creatinine, creatine kinase, cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and the decreased levels of estimated glomerular filtration rate were obviously observed. This patient was started on L-T4 (75 and 100 µg, alternate). OUTCOMES AND LESSONS: Following a two-month treatment, the serum creatine kinase level decreased to within normal range. The estimated glomerular filtration rate level was restored, and the serum creatinine level was down-regulated, although slightly higher than the normal range. L-T4 partially reversed HT-induced the disorders of muscle, renal function, and lipid profile of this patient and remarkably alleviated her HT-related symptoms.

Lentinan Ameliorates ß-Hydroxybutyrate-Induced Lipid Metabolism Disorder in Bovine Hepatocytes by Upregulating the Expression of Acetyl-coenzyme A Acetyltransferase 2.

Ketosis in dairy cows is often accompanied by the dysregulation of lipid homeostasis in the liver. Acetyl-coenzyme A acetyltransferase 2 (ACAT2) is specifically expressed in the liver and is important for regulating lipid homeostasis in ketotic cows. Lentinan (LNT) has a wide range of pharmacological activities, and this study investigates the protective effects of LNT on ß-hydroxybutyrate (BHBA)-induced lipid metabolism disorder in bovine hepatocytes (BHECs) and elucidates the underlying mechanisms. BHECs were first pretreated with LNT to investigate the effect of LNT on BHBA-induced lipid metabolism disorder in BHECs. ACAT2 was then silenced or overexpressed to investigate whether this mediated the protective action of LNT against BHBA-induced lipid metabolism disorder in BHECs. Finally, BHECs were treated with LNT after silencing ACAT2 to investigate the interaction between LNT and ACAT2. LNT pretreatment effectively enhanced the synthesis and absorption of cholesterol, inhibited the synthesis of triglycerides, increased the expression of ACAT2, and elevated the contents of very low-density lipoprotein and low-density lipoprotein cholesterol, thereby ameliorating BHBA-induced lipid metabolism disorder in BHECs. The overexpression of ACAT2 achieved a comparable effect to LNT pretreatment, whereas the silencing of ACAT2 aggravated the effect of BHBA on inducing disorder in lipid metabolism in BHECs. Moreover, the protective effect of LNT against lipid metabolism disorder in BHBA-induced BHECs was abrogated upon silencing of ACAT2. Thus, LNT, as a natural protective agent, can enhance the regulatory capacity of BHECs in maintaining lipid homeostasis by upregulating ACAT2 expression, thereby ameliorating the BHBA-induced lipid metabolism disorder.

Salusin­α alleviates lipid metabolism disorders via regulation of the downstream lipogenesis genes through the LKB1/AMPK pathway.

Lipid metabolism disorders are a major cause of several chronic metabolic diseases which seriously affect public health. Salusin­α, a vasoactive peptide, has been shown to attenuate lipid metabolism disorders, although its mechanism of action has not been reported. To investigate the effects and potential mechanisms of Salusin­α on lipid metabolism, Salusin­α was overexpressed or knocked down using lentiviral vectors. Hepatocyte steatosis was induced by free fatty acid (FFA) after lentiviral transfection into HepG2 cells. The degree of lipid accumulation was assessed using Oil Red O staining and by measuring several biochemical indices. Subsequently, bioinformatics was used to analyze the signaling pathways that may have been involved in lipid metabolism disorders. Finally, semi­quantitative PCR and western blotting were used to verify the involvement of the liver kinase B1 (LKB1)/AMPK pathway. Compound C, an inhibitor of AMPK, was used to confirm this mechanism's involvement further. The results showed that Salusin­α significantly attenuated lipid accumulation, inflammation and oxidative stress. In addition, Salusin­α increased the levels of LKB1 and AMPK, which inhibited the expression of sterol regulatory element binding protein­1c, fatty acid synthase and acetyl­CoA carboxylase. The addition of Compound C abrogated the Salusin­α­mediated regulation of AMPK on downstream signaling molecules. In summary, overexpression of Salusin­α activated the LKB1/AMPK pathway, which in turn inhibited lipid accumulation in HepG2 cells. This provides insights into the potential mechanism underlying the mechanism by which Salusin­α ameliorates lipid metabolism disorders while identifying a potential therapeutic target.

Total saponins from Panax japonicus regulated the intestinal microbiota to alleviate lipid metabolism disorders in aging mice.

Total saponins from Panax japonicus (TSPJ) have many beneficial physiological activities, particularly in alleviating the damages of aging and abnormal lipid metabolism. This work used mice models to investigate if TSPJ reduced obesity and regulated metabolic functions via the intestinal microbiota, the disturbance of which has been shown to cause aging-related diseases. The results showed that TSPJ significantly reduced the weight and blood lipid level of aging mice. Further analyses showed that TSPJ significantly inhibited adipogenesis, changed the composition of the intestinal flora, and protected the integrity of the intestinal barrier. It was inferred from the accumulated experimental data that TSPJ helped to combat obesity in aging mice by regulating the intestinal microbiota and promoting microbial metabolism.

Jingangteng capsules ameliorate liver lipid disorders in diabetic rats by regulating microflora imbalances, metabolic disorders, and farnesoid X receptor.

BACKGROUND: The plant Smilax china L., also known as Jingangteng, is suspected of regulating glucose and lipid metabolism. Jingangteng capsules (JGTCs) are commonly used to treat gynecological inflammation in clinical practice. However, it is not clear whether JGTCs can regulate glucose and lipid metabolism, and the mechanism is unclear. PURPOSE: To investigate the impact and mechanism of action of JGTCs on diabetes and liver lipid disorders in rats. METHODS: The chemical constituents of JGTCs were examined using ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. A high-fat diet and streptozotocin-induced diabetes model was used to evaluate anti-diabetic effects by assessing blood glucose and lipid levels and liver function. The mechanism was explored using fecal 16S rRNA gene sequencing and metabolomics profiling, reverse transcription-quantiative polymerase chain reaction (RT-qPCR), and Western blot analysis. RESULTS: Thirty-three components were identified in JGTCs. The serological and histomorphological assays revealed that JGTC treatment reduced levels of blood glucose and lipids, aspartate aminotransferase, alanine aminotransferase, and lipid accumulation in the liver of diabetic rats. According to 16S rDNA sequencing, JGTCs improved species richness and diversity in diabetic rats' intestinal flora and restored 22 dysregulated bacteria to control levels. Fecal metabolomics analysis showed that the altered fecal metabolites were rich in metabolites, such as histidine, taurine, low taurine, tryptophan, glycerophospholipid, and arginine. Serum metabolomics analysis indicated that serum metabolites were enriched in the metabolism of glycerophospholipids, fructose and mannose, galactose, linoleic acid, sphingolipids, histidine, valine, leucine and isoleucine biosynthesis, and tryptophan metabolism. Heatmaps revealed a strong correlation between metabolic parameters and gut microbial phylotypes. Molecular biology assays showed that JGTC treatment reversed the decreased expression of farnesoid X receptor (FXR) in the liver of diabetic rats and inhibited the expression of lipogenic genes (Srebp1c and FAS) as well as inflammation-related genes (interleukin (IL)-ß, tumor necrosis factor (TNF)-α, and IL-6). Liver metabolomics analysis indicated that JGTC could significantly regulate a significant number of bile acid metabolites associated with FXR, such as glyco-beta-muricholic acid, glycocholic acid, tauro-beta-muricholic acid, and tauro-gamma-muricholic acid. CONCLUSIONS: This was the first study to investigate the mechanisms of JGTCs' effects on liver lipid disorders in diabetic rats. JGTCs inhibited liver lipid accumulation and inflammatory responses in diabetic rats by affecting intestinal flora and metabolic disorders and regulating FXR-fat synthesis-related pathways to alleviate diabetic lipid disorders.

Polystyrene Nanoplastics Induce Lipid Metabolism Disorder by Activating the PERK-ATF4 Signaling Pathway in Mice.

In recent years, the study of microplastics (MPs) and nanoplastics (NPs) and their effects on human health has gained significant attention. The impacts of NPs on lipid metabolism and the specific mechanisms involved remain poorly understood. To address this, we utilized high-throughput sequencing and molecular biology techniques to investigate how endoplasmic reticulum (ER) stress might affect hepatic lipid metabolism in the presence of polystyrene nanoplastics (PS-NPs). Our findings suggest that PS-NPs activate the PERK-ATF4 signaling pathway, which in turn upregulates the expression of genes related to lipid synthesis via the ATF4-PPARγ/SREBP-1 pathway. This activation leads to an abnormal accumulation of lipid droplets in the liver. 4-PBA, a known ER stress inhibitor, was found to mitigate the PS-NPs-induced lipid metabolism disorder. These results demonstrate the hepatotoxic effects of PS-NPs and clarify the mechanisms of abnormal lipid metabolism induced by PS-NPs.

A narrative review on the mechanism of natural flavonoids in improving glucolipid metabolism disorders.

Glucolipid metabolism disorder (GLMD) is a complex chronic disease characterized by glucose and lipid metabolism disorders with a complex and diverse etiology and rapidly increasing incidence. Many studies have identified the role of flavonoids in ameliorating GLMD, with mechanisms related to peroxisome proliferator-activated receptors, nuclear factor kappa-B, AMP-activated protein kinase, nuclear factor (erythroid-derived 2)-like 2, glucose transporter type 4, and phosphatidylinositol-3-kinase/protein kinase B pathway. However, a comprehensive summary of the flavonoid effects on GLMD is lacking. This study reviewed the roles and mechanisms of natural flavonoids with different structures in the treatment of GLMD reported globally in the past 5 years and provides a reference for developing flavonoids as drugs for treating GLMD.

Restoration of HMGCS2-mediated ketogenesis alleviates tacrolimus-induced hepatic lipid metabolism disorder.

Tacrolimus, one of the macrolide calcineurin inhibitors, is the most frequently used immunosuppressant after transplantation. Long-term administration of tacrolimus leads to dyslipidemia and affects liver lipid metabolism. In this study, we investigated the mode of action and underlying mechanisms of this adverse reaction. Mice were administered tacrolimus (2.5 mg·kg-1·d-1, i.g.) for 10 weeks, then euthanized; the blood samples and liver tissues were collected for analyses. We showed that tacrolimus administration induced significant dyslipidemia and lipid deposition in mouse liver. Dyslipidemia was also observed in heart or kidney transplantation patients treated with tacrolimus. We demonstrated that tacrolimus did not directly induce de novo synthesis of fatty acids, but markedly decreased fatty acid oxidation (FAO) in AML12 cells. Furthermore, we showed that tacrolimus dramatically decreased the expression of HMGCS2, the rate-limiting enzyme of ketogenesis, with decreased ketogenesis in AML12 cells, which was responsible for lipid deposition in normal hepatocytes. Moreover, we revealed that tacrolimus inhibited forkhead box protein O1 (FoxO1) nuclear translocation by promoting FKBP51-FoxO1 complex formation, thus reducing FoxO1 binding to the HMGCS2 promoter and its transcription ability in AML12 cells. The loss of HMGCS2 induced by tacrolimus caused decreased ketogenesis and increased acetyl-CoA accumulation, which promoted mitochondrial protein acetylation, thereby resulting in FAO function inhibition. Liver-specific HMGCS2 overexpression via tail intravenous injection of AAV8-TBG-HMGCS2 construct reversed tacrolimus-induced mitochondrial protein acetylation and FAO inhibition, thus removing the lipid deposition in hepatocytes. Collectively, this study demonstrates a novel mechanism of liver lipid deposition and hyperlipidemia induced by long-term administration of tacrolimus, resulted from the loss of HMGCS2-mediated ketogenesis and subsequent FAO inhibition, providing an alternative target for reversing tacrolimus-induced adverse reaction.

Regulatory effects of Astragalus membranaceus polysaccharides on lipid metabolism disorders induced by a high-fat diet in spotted sea bass (Lateolabrax maculatus).

This study evaluated the regulatory effects of Astragalus membranaceus polysaccharides (AMP) on lipid metabolism disorders induced by a high-fat diet (HFD) in spotted sea bass (Lateolabrax maculatus). Compared with the normal diets (10 % lipids), diets containing 15 % lipid levels were used as the high-fat diet (HFD). Three levels of the AMP (0.06 %, 0.08 %, 0.10 %) were added in the HFD and used as experimental diets. A total of 375 spotted sea bass (average weight 3.00 ± 0.01 g) were divided into 15 tanks and deemed as 5 groups, with each tank containing 25 fish. Fish in each group were fed with different diets for 56 days. After feeding, the HFD induced lipid metabolism disorders in fish, as evidenced by elevated serum lipids, malonaldehyde levels, and more severe liver damage. The AMP alleviated the HFD-induced liver damage, as evidenced by the reduced severity of liver histological lesions and malonaldehyde levels. The low-density lipoprotein cholesterol was reduced, and the expression of FAS and PPAR-α were down and up-regulated, respectively. However, the AMP had a limited ability to affect the serum lipids and abdominal fat percentage. These results reveal the potential of the AMP used in aquaculture to regulate lipid metabolism disorders induced by the HFD.

Regulatory patterns of Chinese patent medicine for lipid metabolism disorders in patients with type 2 diabetes mellitus complicated by ischemic stroke: A systematic review and network meta-analysis.

BACKGROUND: To investigate the regulatory patterns of Chinese patent medicine (CPM) interventions on lipid metabolism disorders in patients with type 2 diabetes mellitus (T2DM) complicated by ischemic stroke. METHODS: Two researchers independently searched 8 major databases and created a comprehensive database containing all randomized controlled trials (RCTs) that investigated the application of "blood-activating and stasis-removing" CPM in the treatment of stroke combined with T2DM until October 1, 2022. The collected data were compiled and organized in Excel. Quality assessment was performed using the Cochrane 5.3 bias risk assessment tool, and the network meta-analysis was conducted using R software. RESULTS: A total of 12 articles were included in the final analysis, covering 4 types of CPM: Naoxintong Capsules (NXT), Tongmai Jiangtang Capsules, Tongxinluo Capsules (TXL), and Yindan Xinnaotong Soft Capsules. Among these, CPM formulations containing herbs with blood-activating and stasis-removing properties were the most commonly used. The results of the network meta-analysis are as follows: (1) the combination of 3 CPM formulations showed superior efficacy in improving total cholesterol levels compared to conventional Western medicine treatment (CT). In particular, Yindan Xinnaotong Soft Capsules + CT (surface under the cumulative ranking curve [SUCRA] = 97.24%) demonstrated the highest efficacy, followed by NXT + CT (SUCRA = 66.23%), and then TXL + CT (SUCRA = 55.16%). (2) TXL + CT treatment exhibited the most promising efficacy in improving triglyceride levels (P < .05), while the effects of the other 3 CPM formulations were not statistically significant. (3) In terms of improving low-density lipoprotein levels, NXT + CT (SUCRA = 82.27%) showed better efficacy than TXL + CT (SUCRA = 73.99%), while the effects of the other 2 CPM formulations were not statistically significant. (4) The combination of CPM formulations and CT resulted in a lower incidence of adverse reactions compared to CT (P < .05). CONCLUSION: The treatment of patients with T2DM complicated by ischemic stroke commonly involved the use of "blood-activating and stasis-removing" herbal medicines. These herbal medicines have shown effectiveness in regulating patients' blood lipid levels. However, it is crucial to acknowledge that the analysis was influenced by variations in the number and quality of RCTs involving different CPM formulations. Therefore, additional validation through large-scale, high-quality RCT studies is required.

Extract of Gualou-Xiebai Herb Pair Improves Lipid Metabolism Disorders by Enhancing the Reverse Cholesterol Transport in Atherosclerosis Mice.

BACKGROUND: Gualou is derived from the fruit of Trichosanthes kirilowii Maxim, while Xiebai from the bulbs of Allium macrostemon Bunge. Gualou and Xiebai herb pair (2:1) is widely used in clinical practice to treat atherosclerotic cardiovascular diseases. However, the mechanism underlying its potential activity on atherosclerosis (AS) has not been fully elucidated. METHODS: The extract of Gualou-Xiebai herb pair (GXE) was prepared from Gualou (80 g) and Xiebai (40 g) by continuous refluxing with 50% ethanol for 2 h at 80°C. In vivo, ApoE-/- mice were fed a high-fat diet (HFD) for 10 weeks to induce an AS model, and then the mice were treated with GXE (3, 6, 12 g/kg) or atorvastatin (10 mg/kg) via oral gavage. Besides, RAW264.7 macrophages were stimulated by ox-LDL to establish a foam cell model in vitro. RESULTS: GXE suppressed plaque formation, regulated plasma lipids, and promoted liver lipid clearance in AS mice. In addition, 0.5, 1, and 2 mg/mL GXE significantly reduced the TC and FC levels in ox-LDL (50 µg/mL)-stimulated foam cells. GXE increased cholesterol efflux from the foam cells to ApoA-1 and HDL, and enhanced the protein expressions of ABCA1, ABCG1, and SR-BI, which were reversed by the PPARγ inhibitor. Meanwhile, GXE increased the LCAT levels, decreased the lipid levels and increased the TBA levels in the liver of AS mice. Molecular docking indicated that some compounds in GXE showed favorable binding energy with PPARγ, LCAT and CYP7A1 proteins, especially apigenin-7-O-ß-D-glucoside and quercetin. CONCLUSION: In summary, our results suggested that GXE improved lipid metabolism disorders by enhancing RCT, providing a scientific basis for the clinical use of GXE in AS treatment.

Tolypocladium sinense Mycelium Polysaccharide Alleviates Obesity, Lipid Metabolism Disorder, and Inflammation Caused by High Fat Diet via Improving Intestinal Barrier and Modulating Gut Microbiota.

SCOPE: Tolypocladium sinense is a fungus isolated from Cordyceps. Cordyceps has some medicinal value and is also a daily health care product. This study explores the preventive effects of T. sinense mycelium polysaccharide (TSMP) on high-fat diet-induced obesity and chronic inflammation in mice. METHODS AND RESULTS: Here, the study establishes an obese mouse model induced by high-fat diet. In this study, the mice are administered TSMP daily basis to evaluate its effect on alleviating obesity. The results show that TSMP can significantly inhibit obesity and alleviate dyslipidemia by regulating the expression of lipid metabolism-related genes such as liver kinase B1 (LKB1), phosphorylated AMP-activated protein kinase (pAMPK), peroxisome proliferator activated receptor α (PPARα), fatty acid synthase (FAS), and hydroxymethylglutaryl-CoA reductase (HMGCR) in the liver. TSMP can increase the protein expression of zona occludens-1 (ZO-1), Occludin, and Claudin-1 in the colon, improve the intestinal barrier dysfunction, and reduce the level of serum LPS, thereby reducing the inflammatory response. 16S rDNA sequencing shows that TSMP alters the intestinal microbiota by increasing the relative abundance of Akkermansia, Lactobacillus, and Prevotellaceae_NK3B31_group, while decreasing the relative abundance of Faecalibaculum. CONCLUSION: The findings show that TSMP can inhibit obesity and alleviates obesity-related lipid metabolism disorders, inflammatory responses, and oxidative stress by modulating the gut microbiota and improving intestinal barrier.

Myricanol improves metabolic profiles in dexamethasone induced lipid and protein metabolism disorders in mice.

Myricanol (MY) is one of the main active components from bark of Myrica Rubra. It is demonstrated that MY rescues dexamethasone (DEX)-induced muscle dysfunction via activating silent information regulator 1 (SIRT1) and increasing adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation. Since SIRT1 and AMPK are widely involved in the metabolism of nutrients, we speculated that MY may exert beneficial effects on DEX-induced metabolic disorders. This study for the first time applied widely targeted metabolomics to investigate the beneficial effects of MY on glucose, lipids, and protein metabolism in DEX-induced metabolic abnormality in mice. The results showed that MY significantly reversed DEX-induced soleus and gastrocnemius muscle weight loss, muscle fiber damage, and muscle strength loss. MY alleviated DEX-induced metabolic disorders by increasing SIRT1 and glucose transporter type 4 (GLUT4) expressions. Additionally, myricanol prevented muscle cell apoptosis and atrophy by inhibiting caspase 3 cleavages and muscle ring-finger protein-1 (MuRF1) expression. Metabolomics showed that MY treatment reversed the serum content of carnitine ph-C1, palmitoleic acid, PS (16:0_17:0), PC (14:0_20:5), PE (P-18:1_16:1), Cer (t18:2/38:1(2OH)), four amino acids and their metabolites, and 16 glycerolipids in DEX mice. Kyoto encyclopedia of genes and genomes (KEGG) and metabolic set enrichment analysis (MSEA) analysis revealed that MY mainly affected metabolic pathways, glycerolipid metabolism, lipolysis, fat digestion and absorption, lipid and atherosclerosis, and cholesterol metabolism pathways through regulation of metabolites involved in glutathione, butanoate, vitamin B6, glycine, serine and threonine, arachidonic acid, and riboflavin metabolism. Collectively, MY can be used as an attractive therapeutic agent for DEX-induced metabolic abnormalities.

Cyclodextrins as therapeutic drugs for treating lipid metabolism disorders.

OBJECTIVE: This study sought to systematically compare the efficacy and mechanism of cyclodextrins as drug interventions in lipid metabolism diseases, potentially providing ideas for subsequent research directions and clinical applications. METHODS: We used the bibliometric method for feature mining, applied VOSviewer software for clustering analysis, and applied content analysis for objective descriptions and accurate analysis. RESULTS: (1) We collected more than 50 studies, which is the basic database of this study. (2) The academic bubble map showed that this research area was popular in the United States. (3) Cluster analysis showed that the intensively studied diseases in this field were Niemann-Pick type C (NPC), atherosclerosis (AS), and obesity. The hot-spot cyclodextrin types were HP-ß-CD. (4) Literature measurement revealed the involvement of 15 types of lipid metabolism diseases. Among them, NPC, diabetes, and obesity were studied in clinical trials. Dyslipidemia and AS have been reported relatively more frequently in animal experiments. The studies of cellular experiments provide insight into the molecular mechanisms that intervene in lipid metabolism diseases from multiple perspectives. The exploration of the molecular mechanisms by which cyclodextrins exert their pharmacological effects mainly revolves around lipid metabolism. CONCLUSION: It is worthwhile to investigate the role and mechanism of cyclodextrins in other lipid metabolism diseases. The potential efficacy evaluation of cyclodextrins as pharmaceutical drugs for oral or injectable formulations is less studied and may become a new focus in the future.

Integrative proteomic and metabonomic profiling elucidates amino acid and lipid metabolism disorder in CA-MRSA-infected breast abscesses.

Objective: Bacterial culture and drug sensitivity testing have been the gold standard for confirming community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in breast abscess with a long history. However, these tests may delay treatment and increase the risk of nosocomial infections. To handle and improve this critical situation, this study aimed to explore biomarkers that could facilitate the rapid diagnosis of CA-MRSA infection. Methods: This study for the first time applied label-free quantitative proteomics and non-targeted metabonomics to identify potential differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs) in breast abscess infected with CA-MRSA compared to methicillin-susceptible S. aureus (MSSA). The two omics data were integrated and analyzed using bioinformatics, and the results were validated using Parallel Reaction Monitoring (PRM). Receiver operating characteristic (ROC) curves were generated to evaluate the predictive efficiency of the identified biomarkers for diagnosing CA-MRSA infection. Results: After using the above-mentioned strategies, 109 DEPs were identified, out of which 86 were upregulated and 23 were downregulated. Additionally, a total of 61 and 26 DEMs were initially screened in the positive and negative ion modes, respectively. A conjoint analysis indicated that the amino acid metabolism, glycosphingolipid biosynthesis, and glycerophospholipid metabolism pathways were co-enriched by the upstream DEPs and downstream DEMs, which may be involved in structuring the related network of CA-MRSA infection. Furthermore, three significant DEMs, namely, indole-3-acetic acid, L-(-)-methionine, and D-sedoheptulose 7-phosphate, displayed good discriminative abilities in early identification of CA-MRSA infection in ROC analysis. Conclusion: As there is limited high-quality evidence and multiple omics research in this field, the explored candidate biomarkers and pathways may provide new insights into the early diagnosis and drug resistance mechanisms of CA-MRSA infection in Chinese women.

Quercitrin alleviates lipid metabolism disorder in polycystic ovary syndrome-insulin resistance by upregulating PM20D1 in the PI3K/Akt pathway.

BACKGROUND: Abnormal endocrine metabolism caused by polycystic ovary syndrome combined with insulin resistance (PCOS-IR) poses a serious risk to reproductive health in females. Quercitrin is a flavonoid that can efficiently improve both endocrine and metabolic abnormalities. However, it remains unclear if this agent can exert therapeutic effect on PCOS-IR. METHODS: The present study used a combination of metabolomic and bioinformatic methods to screen key molecules and pathways involved in PCOS-IR. A rat model of PCOS-IR and an adipocyte IR model were generated to investigate the role of quercitrin in regulating reproductive endocrine and lipid metabolism processes in PCOS-IR. RESULTS: Peptidase M20 domain containing 1 (PM20D1) was screened using bioinformatics to evaluate its participation in PCOS-IR. PCOS-IR regulation via the PI3K/Akt signaling pathway was also investigated. Experimental analysis showed that PM20D1 levels were reduced in insulin-resistant 3T3-L1 cells and a letrozole PCOS-IR rat model. Reproductive function was inhibited, and endocrine metabolism was abnormal. The loss of adipocyte PM20D1 aggravated IR. In addition, PM20D1 and PI3K interacted with each other in the PCOS-IR model. Furthermore, the PI3K/Akt signaling pathway was shown to participate in lipid metabolism disorders and PCOS-IR regulation. Quercitrin reversed these reproductive and metabolic disorders. CONCLUSION: PM20D1 and PI3K/Akt were required for lipolysis and endocrine regulation in PCOS-IR to restore ovarian function and maintain normal endocrine metabolism. By upregulating the expression of PM20D1, quercitrin activated the PI3K/Akt signaling pathway, improved adipocyte catabolism, corrected reproductive and metabolic abnormalities, and had a therapeutic effect on PCOS-IR.

Eucommia bark/leaf extract improves HFD-induced lipid metabolism disorders via targeting gut microbiota to activate the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis.

BACKGROUND: The bark of Eucommia ulmoides (a perennial deciduous tree termed eucommia hereafter) has anti-hyperlipidemia effects due to its bioactive components. However, the slow growth of eucommia bark leads to a deficit in this resource. Studies have shown that eucommia leaf has bioactive components similar to those of eucommia bark and anti-hyperlipidemia effects. At present, the strength of the anti-hyperlipidemia effect of eucommia bark and eucommia leaf has not been reported. Their interaction with the gut microbiota and the mechanism by which the gut microbiota exerts anti-hyperlipidemia effects are unclear. PURPOSES: Through fecal microbiota transplantation (FMT) experiments, this study aimed to investigate the mechanism by which fecal bacteria suspensions containing chlorogenic acid (CGA), eucommia bark extract (EBE), and eucommia leaves extract (ELE) improve high-fat diet (HFD)-induced lipid metabolism disorders. Difference in anti-hyperlipidemia effects between EBE and ELE and exploring an eucommia bark substitute to improve the sustainable utilization of eucommia were also evaluated. RESULTS: EBE and ELE contain eight identical bioactive ingredients, and fecal bacteria suspensions containing EBE and ELE significantly improved HFD-induced lipid metabolism disorders and elevated blood glucose levels. The fecal bacteria suspension of healthy mice containing CGA, EBE, and ELE significantly reduced the relative abundance of Erysipelothrichaceae and Ruminococcaceae and promoted short chain fatty acids (SCFAs) production thereby activating the expression of the SCFA. G protein-coupled receptor 43 (GPR43) gene in colon and epididymal fat tissues. In addition, fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE significantly activated fasting-induced adipose factor (Fiaf) gene expression in colon tissue and inhibited the secretion of lipoprotein lipase (LPL) in liver tissue, thereby inhibiting the synthesis of triglycerides (TG). Changed in the Erysipelotrichaceae and Ruminococcaceae relative abundances were significantly correlated with these target genes. Thus, regulating the abundance of the Erysipelotrichaceae and Ruminococcaceae could serve as a potential target for the role of fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE in the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis. In addition, regarding HFD-induced lipid metabolism disorders and gut microbiota structural disorders, we found no significant difference between ELE and EBE. CONCLUSIONS: Our FMT experiments evidenced that EBE and ELE improve lipid metabolism disorders by regulating the gut microbiota, providing a new pathway for treating hyperlipidemia using eucommia dietary therapy. There was no significant difference in the anti-hyperlipidemia effects of ELE and EBE; thus, eucommia leaf could replace eucommia bark in traditional Chinese medicine, so as to achieve a sustainable utilization of eucommia resources.

Lactobacillus-fermented yogurt exerts hypoglycemic, hypocholesterolemic, and anti-inflammatory activities in STZ-induced diabetic Wistar rats.

Hyperglycemia is a symptom of type 2 diabetes mellitus, a chronic metabolic disease characterized by elevated blood glucose concentrations. Antidiabetic drugs are common treatments for this metabolic disorder; however, they may have unpleasant side effects. This study hypothesized that probiotic fermented products could preserve nutritional value, maintain metabolic homeostasis, and attenuate the inflammatory response associated with diabetes while reducing side effects. Lactobacillus plantarum KU985438 and Lactobacillus rhamnosus KU985439 showed the lowest alfa-amylase enzyme (α-amylase) activity among 8 lactobacilli tested. These 2 strains were used to develop functional fermented milk products, and their antidiabetic efficacy was tested in induced diabetic Wistar rats. The treatment of diabetic rats with L. plantarum KU985438 or L. rhamnosus KU985439 fermented yogurt resulted in a considerable reduction in blood glucose concentrations (136.79% and 145.17%, respectively) and α-amylase concentrations (56.84% and 56.84%, respectively) compared with conventional treatments. Diabetes relief began after 4 days of yogurt consumption compared with drug-based treatment. Significant improvements in both liver and kidney enzyme concentrations were also observed, in addition to a significant increase in high-density lipoprotein cholesterol concentrations and improved lipid profiles. Inhibition in nuclear factor κB and an increase in Bcl-2 concentrations were also detected. Histopathological examination of both hepatic and pancreatic cells revealed the positive effects of the studied treatment compared with standard treatment. Therefore, the selected Lactobacilli, which has hypoglycemic potential, could be used to produce functional nutraceutical antidiabetic supplements.