Glycolipid Metabolism Research Articles

Common molecular basis for MASH and hepatitis C revealed via systems biology approach

BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is characterized by liver inflammation and damage caused by a buildup of fat in the liver. Hepatitis C, caused by hepatitis C virus (HCV), is a disease that can lead to liver cirrhosis, liver cancer, and liver failure. MASH and hepatitis C are the common causes of liver cirrhosis and hepatocellular carcinoma. Several studies have shown that hepatic steatosis is also a common histological feature of liver in HCV infected patients. However, the common molecular basis for MASH and hepatitis C remains poorly understood.MethodsFirstly, differentially expressed genes (DEGs) for MASH and hepatitis C were extracted from the GSE89632, GSE164760 and GSE14323 datasets. Subsequently, the common DEGs shared among these datasets were determined using the Venn diagram. Next, a protein-protein interaction (PPI) network was constructed based on the common DEGs and the hub genes were extracted. Then, gene ontology (GO) and pathway analysis of the common DEGs were performed. Furthermore, transcription factors (TFs) and miRNAs regulatory networks were constructed, and drug candidates were identified. After the MASH and hepatitis C cell model was treated with predicted drug, the expression levels of the signature genes were measured by qRT-PCR and ELISA.Results866 common DEGs were identified in MASH and hepatitis C. The GO analysis showed that the most significantly enriched biological process of the DEGs was the positive regulation of cytokine production. 10 hub genes, including STAT1, CCL2, ITGAM, PTPRC, CXCL9, IL15, SELL, VCAM1, TLR4 and CCL5, were selected from the PPI network. By constructing the TF-gene and miRNA-gene network, most prominent TFs and miRNAs were screened out. Potential drugs screening shows that Budesonide and Dinoprostone may benefit patients, and cellular experiments showed that Budesonide effectively inhibited the expression of genes related to glycolipid metabolism, fibrosis, and inflammatory factors.ConclusionWe extracted 10 hub genes between MASH and hepatitis C, and performed a series of analyses on the genes. Molecular docking and in vitro studies have revealed that Budesonide can effectively suppress the progression of MASH and hepatitis C. This study can provide novel insights into the potential drug targets and biomarkers for MASH and hepatitis C.

Low phosphorus causes hepatic energy metabolism disorder through Dynamin-related protein 1-mediated mitochondrial fission in fish

BackgroundLow phosphorus (LP) diets perturb hepatic energy metabolism homeostasis in fish. However, the specific mechanisms in LP-induced hepatic energy metabolism disorders remain to be fully elucidated. ObjectivesThis study sought to elucidate the underlying mechanisms of mitochondria involved in LP-induced energy metabolism disorders. MethodsSpotted seabass were fed diets with 0.72% (S-AP, control) or 0.36% (S-LP) available phosphorus for 10 weeks. Drp1 was knocked down or protein kinase A (PKA) was activated using 8Br-cAMP (5 μM, a PKA activator) in spotted seabass hepatocytes under LP medium. Zebrafish were fed Z-LP diets (0.30% available phosphorus) containing Mdivi-1 (5 mg/kg, a Drp1 inhibitor) or 8Br-cAMP (0.5 mg/kg) for 6 weeks. Biochemical and molecular parameters, along with transmission electron microscopy and immunofluorescence, were used to assess hepatic glycolipid metabolism, mitochondrial function and morphology. ResultsSpotted seabass fed S-LP diets showed reduced ATP (0.52-fold) and cyclic adenosine monophosphate (cAMP) (0.52-fold) levels, along with reduced Drp1 (s582) (0.38-fold) and PKA (0.61-fold) phosphorylation levels in the liver compared with those fed S-AP diets (P < 0.05). Drp1 knockdown elevated ATP levels (1.99-fold), decreased mitochondrial DRP1 protein levels (0.45-fold), and increased mitochondrial aspect ratio (1.82-fold) in LP-treated hepatocytes (P < 0.05). Furthermore, 8Br-cAMP-treated hepatocytes exhibited higher PKA phosphorylation (2.85-fold), ATP levels (1.60-fold), and mitochondrial aspect ratio (2.00-fold), along with decreased mitochondrial DRP1 protein levels (0.29-fold) under LP medium (P < 0.05). However, mutating s582 to alanine mimic Drp1 dephosphorylation decreased ATP levels (0.63-fold) and mitochondrial aspect ratio (0.53-fold) in 8Br-cAMP-treated hepatocytes (P < 0.05). In addition, zebrafish were fed Z-LP diets containing Mdivi-1 or 8Br-cAMP had higher ATP levels (3.44-fold or 1.98-fold) than that fed Z-LP diets (P < 0.05). ConclusionsThese findings provide a potential mechanistic elucidation for LP-induced energy metabolism disorders through the cAMP/PKA/Drp1-mediated mitochondrial fission signaling pathway.

Improvement in Glycolipid Metabolism Parameters After Supplementing Fish Oil-Derived Omega-3 Fatty Acids Is Associated with Gut Microbiota and Lipid Metabolites in Type 2 Diabetes Mellitus

Improvement in Glycolipid Metabolism Parameters After Supplementing Fish Oil-Derived Omega-3 Fatty Acids Is Associated with Gut Microbiota and Lipid Metabolites in Type 2 Diabetes Mellitus

Dynamic Hydration and Viscosity Control of Konjac Glucomannan Enhance Long-Term Antiobesity Effects by Reducing Food Intake in High-Fat-Diet-Fed Mice.

The purpose of this study was to investigate the necessity and importance of dynamic hydration rate and ultimate viscosity control of konjac glucomannan (KGM) for long-term antiobesity effects in C57BL/6J mice on high-fat (HF) diets. KGM supplementation effectively attenuated HF-diet-induced increases in body and tissue weights. The hydration rate and viscosity changes of KGM in the digestive tract were found to have marked impacts on antiobesity effects. KGM with medium hydration and viscosity slowed gastric emptying and intestinal transit, leading to prolonged presence in the lower ileum, increased satiety-related hormones (GLP-1 and PYY), and an 18.27% reduction in daily food intake over 10 weeks (p < 0.05). This resulted in the greatest reduction in weight gain among HF-fed mice. In contrast, KGM with faster hydration and higher viscosity provided only short-term satiety due to rapid dilution. Furthermore, KGM improved metabolic health and altered glycolipid metabolism gene transcription while enriching beneficial gut bacteria; however, no significant differences were observed among the KGM groups in these effects. These findings highlight that synchronizing KGM's hydration rate and viscosity with digestive processes is crucial for regulating satiety and achieving long-term weight loss.

Loureirin B Ameliorates Glycolipid Metabolism Disorders in Ob/ob Mice by Regulating Bile Acid Levels and Modulating Gut Microbiota Composition.

Loureirin B (LB), an active component of Resina Draconis, exhibits hypoglycemic and hypolipidemic effects; however, its mode of action remains unclear. Here, ob/ob mice were utilized to investigate the effects of LB on the regulation of glucolipid metabolism disorders. Non-targeted metabolomics and 16S rDNA sequencing were performed to elucidate the potential mechanisms involved. Results indicated that LB treatment (45 mg/kg) significantly improved glucose intolerance and insulin resistance, reduced lipid levels, and alleviated hepatic steatosis. Non-targeted metabolomics analysis revealed that LB treatment regulated bile acid levels. Quantification of liver bile acids demonstrated that LB treatment significantly decreased the ratio of 12α-OH to non-12α-OH bile acids in the liver. 16S rDNA sequencing results showed that LB treatment increased the abundance of short-chain fatty acid-producing microbiota while decreasing the abundance of bile salt hydrolase (BSH) enzyme-producing microbiota. In conclusion, LB ameliorates glucolipid metabolism disorders by regulating liver bile acid levels and modulating the composition of the gut microbiota.

Berberine Ameliorates High-fat-induced Insulin Resistance in HepG2 Cells by Modulating PPARs Signaling Pathway.

Berberine (BBR), also known as berberine hydrochloride, was isolated from the rhizomes of the Coptis chinensis. Studies have reported that BBR plays an important role in glycolipid metabolism, including insulin (IR). The targets, and molecular mechanisms of BBR against hyperlipid-induced IR is worthy to be further studied. The related targets of BBR were identified via Pharmmapper database and relevant targets of diabetes were obtained through GeneCards and Online Mendelian Inheritance in Man (OMIM) database. The common targets were employed with the STRING database and visualized with the protein-protein interactions (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to explore the biological progress and pathways. In vitro, human hepatocellular carcinomas (HepG2) cell was used as experimental cell line, and an insulin resistant HepG2 cell model (IR-HepG2) was constructed using free fatty acid induction. After intervention with BBR, glucose consumption and uptake in HepG2 cells were observed. Molecular docking was used to test the interaction between BBR and key targets, and real-time fluorescence quantitative PCR was used to detect the regulatory effect of BBR on related targets. 262 overlapped targets were extracted from BBR and diabetes. In the KEGG enrichment analysis, the peroxisome proliferator activated receptor (PPAR) signaling pathway was included. In vitro experiments, BBR can significantly increase sugar consumption and uptake in IR HepG2 cells, while PPAR inhibitors can weaken the effect of BBR on IR-HepG2. The PPAR signaling pathway is one of the important pathways for BBR to improve high-fat-induced insulin resistance in HepG2 cells.

Highland Barley Alleviates High-Fat Diet-Induced Obesity and Liver Injury Through the IRS2/PI3K/AKT Signaling Pathway in Rats.

Objectives: Highland barley (HB) consumption offers numerous health benefits; however, its impact on glycolipid metabolism abnormalities induced by a high-fat diet remains unclear. Consequently, this study aimed to investigate the therapeutic effects and underlying molecular mechanisms of HB in the context of obesity; Methods: Rats were fed either a high-fat diet (HFD) to induce obesity or a standard diet (SD) for six weeks. The rats in the HFD group were randomly assigned into five groups: HFD+HFD, HFD+SD, and low (30%), medium (45%), and high (60%) doses of the HB diet for an additional ten weeks. Analyses of serum lipid profiles, liver histology, transcriptomes, and untargeted metabolomes were conducted; Results: HB intake resulted in decreased weight gain, reduced feed intake, lower serum triglyceride and cholesterol levels, and diminished hepatic lipid accumulation. It also improved insulin and fasting blood glucose levels, and antioxidant capacity in the HFD-fed rats. Transcriptome analysis revealed that HB supplementation significantly suppressed the HFD-induced increase in the expression of Angptl8, Apof, CYP7A1, GDF15, Marveld1, and Nr0b2. Furthermore, HB supplementation reversed the HFD-induced decrease in Pex11a expression. Untargeted metabolome analysis indicated that HB primarily influenced the pentose phosphate pathway, the Warburg effect, and tryptophan metabolism. Additionally, integrated transcriptome and metabolome analyses demonstrated that the treatments affected the expression of genes associated with glycolipid metabolism, specifically ABCG8, CYP2C12, CYP2C24, CYP7A1, and IRS2. Western blotting confirmed that HB supplementation impacted the IRS2/PI3K/AKT signaling pathway; Conclusions: HB alleviates HFD-induced obesity and liver injury in an obese rat model possibly through the IRS2/PI3K/Akt signaling pathway.

Biological exposure to microplastics and nanoplastics and plastic additives: impairment of glycolipid metabolism and adverse effects on metabolic diseases.

Microplastics and nanoplastics (M-NPs) are widespread pollutants in the environment, posing growing risks to human health and garnering increasing concern from researchers. Due to their small particle size, ease of adsorption, and resistance to degradation, M-NPs can retain and migrate in the environment for long-term periods. Upon entering organisms, M-NPs have been reported to cause inflammation and oxidative stress and result in abnormalities in glycolipid metabolism. Furthermore, research suggests that exposure to M-NPs may act as a causative agent for metabolic and cardiovascular diseases such as diabetes, obesity, and atherosclerosis. This paper aims to review the consequences of exposure to M-NPs on animal and cellular glycolipid metabolism and discusses the disruption of gut microbial homeostasis and the subsequent emergence of insulin resistance. PPAR signaling pathway activation after exposure to M-NPs was found to lead to increased hepatic fat accumulation and impaired lipid metabolism. Additionally, the paper highlights how M-NPs exacerbate the progression of obesity and diabetes in patients, induce damage to vascular endothelial cells, trigger oxidative stress, and contribute to the development of atherosclerosis. Despite the growing concern, the toxicity and molecular mechanism of M-NPs on glycolipid metabolism remain understudied, and effective methods for removing plastic pollutants deposited in the body are yet to be established. These findings provide valuable insights for future research in this field.

Effects of the Fungicide Prothioconazole on Lipid Metabolism in Mice: Whitening Alterations of Brown Adipose Tissue.

With considerable concerns about the associations between metabolic disorders and agricultural biocides, there are scattered data suggesting that the triazole fungicide prothioconazole (PTC) at lower doses than the no observed adverse effect level of 5000 μg/kg/d possibly has the potential to disrupt glycolipid metabolism in mammals. Here, we investigated the effects of 50, 500, and 5000 μg/kg/d of PTC on glycolipid metabolism in mice following 8 weeks of administration via drinking water, with specific attention on brown adipose tissue (BAT) and white adipose tissue (WAT) in addition to the liver. We found that along with the increased serum triglyceride level in the 5000 μg/kg/d group, small fatty vacuoles occurred in livers in all treatment groups, indicating lipid accumulation. No change in WAT was observed, but PTC caused BAT whitening, characterized by adipocyte hypertrophy, more unilocular adipocytes with enlarged lipid droplets, reduced UCP1 levels, and down-regulated Doi2 expression, and even the dose of 50 μg/kg/d was effective. Transcriptomic analysis revealed immune inhibition and circadian rhythm disturbance in BAT from the 5000 μg/kg/d group, which are in agreement with BAT whitening and inactivation. On employing the C3H10T1/2 cells in vitro, we found that PTC treatment concentration-dependently promoted lipid accumulation in brown adipocytes, along with altered expression of thermogenesis-related and circadian genes. Taken together, our study shows that low doses of PTC caused BAT whitening, calling for much attention to the new target by pollutants.

The effect of anti‐imbalance on glycolipid metabolic homeostasis via the liver–gut axis intervened by 3′‐sialyllactose in obese mice

AbstractSialic acid could ameliorate disorders associated with glycolipid metabolism. 3′‐Sialyllactose (3′‐SL), a type of oligosaccharide, contains sialic acid. We examined the effects of 3′‐SL on glycolipid metabolism in obese mice with high fat diet and explore the underlying mechanisms. A total of 160 male C57BL/6J mice were fed with high‐fat diet for 8 weeks to construct obese mice model. Sixty successfully constructed obese mice were randomly divided three 3′‐SL dosage‐dependent groups, one free sialic acid N‐acetylneuraminic acid (Neu5Ac) group, and one blank control group. Each group of obese mice (n = 12) was continuously supplemented by 3′‐SL or Neu5Ac for 10 weeks. Ten‐week 3′‐SL supplementation and Neu5Ac supplementation both yielded remarkedly lower body weight, reduced fat content, increased energy expenditure and active daily exercises with improved glycolipid biomarkers, and attenuated proinflammation. 3′‐SL increased the colonic abundances of Akkermansia, Lactobacillus, and Solibacillus and reduced those of Enterobacter and Enterococcus. Changes were also observed in colonic and liver transcript and metabolites, which were mainly enriched in glycolipid metabolism, ameliorated immune function, and mitigated inflammatory signals, autophagy, bile acid metabolism, and insulin resistance. Akkermansia and Solibacillus were significantly associated with changes in colonic metabolites and transcriptome genes. The liver bile component and glucose metabolites were significantly correlated with transcriptional gene expression in the aforementioned differential pathways. Therefore, 3′‐SL can enhance the gut microbiota, regulate intestinal immunity and bile acid metabolism, reduce liver oxidative stress and autophagy processes, alleviate chronic inflammation levels, and improve islet function and lower blood sugar levels by acting through the gut–liver axis.

Moderate-intensity continuous training and high-intensity interval training alleviate glycolipid metabolism through modulation of gut microbiota and their metabolite SCFAs in diabetic rats

Glucose and lipid metabolism disorders are typical of diabetic patients and are important factors leading to macrovascular and microvascular complications. The aim of this study was to understand the effects of different exercises on glycolipid metabolism in diabetic rats and the role of gut flora in metabolic maintenance. We measured glycolipid metabolic indices and short-chain fatty acids (SCFAs) content and sequenced and analyzed gut microbes after 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) programs in type 2 diabetic rats(T2DM). We found that Enterococcaceae, Enterococcus, Subdoligranulum, Kurthia, Bacillales, and Planococcaceae may be key bacterial taxa related to T2DM and that both programs of exercise regulated the intestinal flora of rats with T2DM, improved their glycolipid metabolism, increased the abundance of SCFA-producing intestinal bacteria, and it was found that the PWY-5676 and P163-PWY pathways which are closely related to production of SCFAs were significantly upregulated in the exercise groups. Notably, MICT appeared to be more effective than HIIT in increasing the homogeneity of rat intestinal flora, enriching species, and increasing acetic acid and butyric acid content. These results suggest that exercise improves glycolipid metabolism in diabetic rats, which may be attributed to alterations in the structure of their intestinal flora.

Research Progress on the Mechanism for Improving Glucose and Lipid Metabolism Disorders Using Phenolic Acid Components from Medicinal and Edible Homologous Plants.

Glucose and lipid metabolism disorders are the core pathological mechanism of a variety of metabolic diseases, and the incidence of related diseases is increasing year by year, which seriously threatens human life and health. Traditional Chinese medicine with medicinal and edible properties refers to Chinese medicinal resources that have both medicinal and edible characteristics. Due to its safety and its health-promoting and medicinal functions, traditional Chinese medicine has received increasing attention in the development of functional health foods. Phenolic acids are important secondary metabolites that are ubiquitous in medicinal and edible homologous plants, and the regulation of glycolipid metabolism is an important activity and plays a key role in many diseases. In this paper, we focus on the alleviation of glycolipid disorders using MEHH phenolic acids, which regulate glucose metabolism and lipid metabolism, improve insulin resistance, inhibit inflammatory responses, alleviate oxidative stress, and regulate intestinal flora; additionally, we summarize the mechanism in order to provide a reference for MEHH phenolic acids in the treatment of glycolipid metabolism diseases.

Hypoglycemic Effect of Rambutan (Nephelium lappaceum L.) Peel Polyphenols on Type 2 Diabetes Mice by Modulating Gut Microbiota and Metabolites.

Type 2 diabetes mellitus (T2DM) is a metabolic disease with a major global public health effect. Rambutan peel polyphenols (RPPs) have been reported to exert hypoglycemic activity. However, few studies have been explored from the viewpoint of gut microbiota and its metabolites. RPPs are administered by gavage to a mice model of T2DM established by using a high-fat diet combined with streptozotocin. It finds that RPPs treatment alleviates hyperglycemia symptoms by improving glucolipid metabolism and liver function. Immunohistochemistry indicates that the antihyperglycemic effect of RPPs is regulated by the IRS-1/PI3K/AKT/GSK3β signaling pathway. RPPs treatment remodels the structure of gut microbiota (Odoribacter, Lachnospiraceae_NK4A136_group, Lactobacillus, Turicibacter, Erysipelatoclostridium, and Tuzzerella) and enriches the metabolites (RPPs-derived urolithins, short-chain fatty acids, dehydrocholic acid, (+)-catechin, dihydroberberine, pterostilbene, and artesunate) associated with diabetes regulation in T2DM mice. The effects of RPPs in ameliorating glycolipid metabolism disorders are correlated with differential gut microbiota and metabolites. The gut microbiota and its metabolites are key targets for the hypoglycemic effects of RPPs.

Qingshen granules inhibits dendritic cell glycolipid metabolism to alleviate renal fibrosis via PI3K-AKT-mTOR pathway

BackgroundQingshen exhibits anti-inflammatory and immunoregulation effects to renal damage. Dendritic cells (DCs) play a critical role in regulating the pathologic inflammatory environment in renal fibrosis (RF). PurposeTo investigate the immune modulation mechanism of qingshen granule (QSG) in RF, particularly focusing on the role of DCs. Methods/Study designAdenine-induced RF animal models were used to study the pharmacological effects of QSG and the immune cells differentiation and function. Glucose uptake, non-esterified fatty acids secretion, mitochondrial membrane potential (MMP) detection, and qPCR were used to explore the effect of QSG to glucose and lipid metabolism in DCs and T cells. The effect of QSG to PI3K-AKT-mTOR axis and the modulation of mTOR to PD-L1 were explored by co-culture experiments, co-immunoprecipitation and western blot assays. The interaction of DCs/CD8+T cells and renal tubular epithelial cells (RTECs) was investigated to demonstrate the direct action and/or the immune-mediated regulation of QSG to RF. The components of QSG in the serum were determined by HPLC. And the effect of active ingredients and formula to DCs and T cells was analyzed by cell experiments in vitro. ResultsQSG reduced nephritic histopathological damage and suppressed the release of proinflammatory cytokines in adenine-induced RF mice. Of note, QSG decreased the levels of CD86, MHC-II, and CCR7 on DCs, while, increased PD-L1 expression on DCs in RF. The results demonstrated that QSG promoted the maturation and inhibited the migration of DCs, and QSG decreased the antigen presenting of DCs to T cells. Additionally, QSG reduced the MMP and glucose/lipid utilization ratio in DCs. QSG also down-regulated the level of targeted metabolic genes included glucose transporter 1 (Glut1), sterol-regulatory element-binding protein 1 (Srebp1), acetyl-CoA carboxylase alpha (Acaca), phosphomevalonate kinase (Pmvk), and up-regulated sirtuin2 (Sirt2) in DCs. In terms of mechanism, QSG inhibited the metabolism-related PI3K-AKT-mTOR pathway, followed by regulating the interaction of mTOR with PD-L1 to enhance the membrane stability of PD-L1. Besides, HPLC analysis identified five active ingredients in QSG. The specific anti-inflammatory and immunosuppressive actions of these ingredients were found to be weaker than QSG as a whole. Finally, inhibiting DC function by QSG disrupted the communication among DCs, T cells, and RTECs. This disruption was associated with low expression of α-smooth muscle actin (α-SMA) and collagen type I (Col-I) in the kidney. ConclusionsQSG inhibits DC metabolism and function via the PI3K-AKT-mTOR pathway to alleviate RF. The study highlights the importance of the specific composition of the formula in targeting DC-mediated immune regulation.

Comparative study of immune responses and intestinal microbiota in the gut-liver axis between wild and farmed pike perch (Sander Lucioperca).

Pike perch (Sander Lucioperca) is a predatory freshwater fish, which is highly popular amongst consumers, owing to its white flesh with a delicate structure and mild flavor. Compared to wild pike perch, the diet of farmed ones has shifted from natural food to artificial feeds. These changes would affect the gut flora of the pike perch. Endogenous metabolites of the intestinal flora are transferred through the gut-liver axis, which affects the physiological functions of the host. By studying wild and farmed individuals of the pike perch, novel insights into the stability of the intestinal flora can be provided. In this study, we measured various immune parameters in the blood, liver and intestine of wild and farmed pike perch using enzyme activity assays and real-time fluorescence quantitative PCR. Gut microbes were also collected for 16S rRNA gene sequencing. Our results showed that the serum low-density lipoprotein cholesterol (LDL-C) levels were twice as high in the wild group as in the farmed group. Furthermore, the activities of glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) in the intestinal tissues of the wild group were 733.91 U/g and 375.35 U/g, which were significantly higher than those of the farmed group. Expression of IL10 in the liver of farmed pike perch was also 4-fold higher than that of wild pike perch. The expression of genes related to the p53-BAX/Bcl2 signaling pathway was higher in both intestinal and liver tissues of wild pike perch compared with farmed. 16S rRNA gene analysis of the gut microflora showed a high relative abundance of Cetobacterium in the gut of farmed pike perch. As a result, our study indicates that dietary differences affect the diversity, composition and relative abundance of the gut flora of the pike perch. Meanwhile, it affects the glycolipid metabolism and immunomodulation of pike perch.

Dietary supplementation with pterostilbene activates the PI3K-AKT-mTOR signalling pathway to alleviate progressive oxidative stress and promote placental nutrient transport

BackgroundProgressive oxidative stress easily occurs as a result of a gradual increase in the intensity of maternal metabolism due to rapid foetal development and increased intensity of lactation. However, studies on the effects of processive oxidative stress on nutrient transport in the placenta have received little attention. The present study was conducted on sows at 85 days of gestation to study the effects of pterostilbene (PTE) on maternal oxidative stress status and placental nutrient transport.ResultsPTE increased the antioxidant capacity and immunoglobulin content in mothers’ blood and milk, reduced the level of inflammatory factors, and improved the nutrient content of milk. PTE also reduced sow backfat loss and the number of weak sons, and increased piglet weaning weight and total weaning litter weight. We subsequently found that PTE enhanced placental glucose and fatty acid transport and further affected glycolipid metabolism by increasing the expression of LAL, PYGM, and Gbe-1, which activated the PI3K phosphorylation pathway. Moreover, PTE addition altered the relative abundance of the Firmicutes, Proteobacteria, Parabacillus, and Bacteroidetes-like RF16 groups in sow faeces. PTE increased the levels of acetate, propionate, butyrate and isovalerate in the faeces.ConclusionsThese findings reveal that the addition of PTE during pregnancy and lactation mitigates the effects of processive oxidative stress on offspring development by altering maternal microbial and placental nutrient transport capacity.Graphical

Eldecalcitol ameliorates diabetic osteoporosis and glucolipid metabolic disorder by promoting Treg cell differentiation through SOCE

Active vitamin D, known for its role in promoting osteoporosis, has immunomodulatory effects according to the latest evidence. Eldecalcitol (ED-71) is a representative of the third-generation novel active vitamin D analogs, and its specific immunological mechanisms in ameliorating diabetic osteoporosis remain unclear. We herein evaluated the therapeutic effects of ED-71 in the context of type 2 diabetes mellitus (T2DM), delving into its underlying mechanisms. In a T2DM mouse model, ED-71 attenuated bone loss and marrow adiposity. Simultaneously, it rectified imbalanced glucose homeostasis and dyslipidemia, ameliorated pancreatic β-cell damage and hepatic glycolipid metabolism disorder. Subsequently, in mice injected with the Treg cell-depleting agent CD25, we observed that the beneficial effects of ED-71 mentioned earlier were partially contingent on the Treg subsets ratio. Mechanistically, ED-71 promoted the differentiation of CD4+ T cells into Treg subsets, facilitating Ca2+ influx and the expression of ORAI1 and STIM1, pivotal proteins in store-operated Ca2+ entry (SOCE). The SOCE inhibitor, 2-APB, partially attenuated the positive effects of ED-71 observed in the above results. Overall, ED-71 regulates SOCE-mediated Treg cell differentiation, accomplishing the dual purpose of simultaneously ameliorating diabetic osteoporosis and glucolipid metabolic disorders, showcasing its potential in osteoimmunity therapy and interventions for diseases involving SOCE.

Arctigenin ameliorates high-fat diet-induced metabolic disorders by reshaping gut microbiota and modulating GPR/HDAC3 and TLR4/NF-κB pathways

BackgroundArctigenin (AG), a phenylpropanoid lignan from the medicinal and food homologous plant Arctium lappa l., is known for its anti-cancer, anti-inflammatory and antioxidant properties. However, the pharmacological effects of AG on metabolic disorders remain limited, and specific mechanisms based on gut microbiota have not been reported. PurposeThis study aimed to evaluate the regulation of glycolipid metabolism by AG in obese mice and investigate the potential mechanisms associated with gut microbes. MethodsThe anti-obesity efficacy of AG was evaluated in high-fat diet (HFD)-fed mice. 16S rRNA gene sequencing and GC–MS were used to detect changes in gut microbes and metabolite levels. Immunohistochemistry, immunofluorescence, and polymerase chain reaction were used to validate the molecular mechanisms of gut microbe-derived metabolites involved in the improvement of intestinal homeostasis and hepatic metabolism by AG. ResultsWe found that AG significantly ameliorated HFD-induced glucolipid metabolism disorders, liver degeneration and the imbalance of macrophage M1/M2 polarization. In addition, AG attenuated intestinal barrier damage, inflammation and imbalance of Th17/Treg immune in HFD mice. Importantly, AG promoted short-chain fatty acid (SCFA)-producing bacteria and SCFA levels, which regulated the G protein-coupled receptor (GPR)41/43 and HDAC3 pathways to induce FOXP3 protein expression and consequently maintained intestinal Th17/Treg immunity. AG also inhibited lipopolysaccharide (LPS) production leading to attenuation of TLR4/NF-κB-mediated intestinal inflammation. Furthermore, AG upregulated intestinal MCT1 protein levels to promote absorption of SCFA and activated the hepatic GPR41/43/109a-AMPK pathway to regulate lipid metabolism, and thus reduced lipid accumulation. ConclusionThis study first demonstrated that AG could modulate the gut microbiota and derived metabolites to repair intestinal damage and regulate hepatic metabolic pathways, thereby ameliorating metabolic disorders induced by HFD. These findings support the great potential of AG as a novel prebiotic to fight obesity and chronic metabolic diseases by targeting the gut microbiota.

Lignan-rich extract from Cinnamomum camphora leaf attenuates metabolic syndrome by modulating glycolipid metabolism and gut microbiota in T2DM mice

BackgroundType 2 diabetes mellitus (T2DM) is a serious metabolic syndrome with high mortality and disability rates globally, which usually caused by unhealthy dietary patterns. Cinnamomum camphora leaf is a traditional Chinese medicinal herb used for attenuating hyperglycemia and digestive disorder, and high level of lignans has been found in C. camphora leaf. PurposeThis study aimed to examine the chemical composition of lignans extracted from C. camphora leaf (LCCL), and illustrate its therapeutic effect and mechanism on T2DM and its concomitant glycolipid metabolic disorder. MethodsThe components of LCCL were separated and purified by silica gel and macroporous adsorption resin, and were distinguished through LC/MS and NMR. The antioxidant activity of LCCL was determined by free radical scavenging assay in vitro; the hypoglycemic and hypolipidemic abilities were evaluated by α-glucosidase, α-amylase and pancreatic lipase inhibition trials, respectively. T2DM model mice were established by high-sugar and high-fat (HSHF) feed together with streptozotocin (STZ) infection, and then grouped to assess the effect of LCCL treatment. Hematoxylin-eosin (H&E), Periodic Acid-Schiff (PAS) and oil red O staining were employed to analyze the histopathology. qRT-PCR assay, 16S rRNA analysis, and western blot were conducted to illuminate the anti-diabetic mechanism of LCCL. Results6 sesamin lignans were identifed from LCCL. The in vitro assays showed strong inhibitive abilities of LCCL with low IC50 on DPPH (33.68 ± 0.54 μg/ml),O2− (39.25 ± 0.61 μg/ml), OH• (45.72 ± 0.72 μg/ml), α-glucosidase (0.82 ± 0.14 mg/ml), α-amylase (0.86 ± 0.11 mg/ml) and pancreatic lipase (0.91 ± 0.12 mg/ml). LCCL treatment (100, 200 and 400 g kg-1mg kg-1) gradually decreased the fasting blood glucose (FBG) and fasting insulin (FINS), improved the glucose and insulin tolerance, down-regulated the homeostasis model assessment insulin resistance (HOMA-IR) indexes, alleviated the hepatic inflammatory response and oxidative stress, promoted the glycogen storage and depleted the fat accumulation in the liver. Besides, LCCL administration alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner, that significantly increased biodiversity, altered the composition of gut microbiota and increased the proportion of Lactobacillus. ConclusionThe lignan-rich extract of C. camphor leaf (LCCL), containing at least 6 lignans compounds, displayed promising antioxidant, hypoglycemic and hypolipidemic activities. The treatment of LCCL alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner. These finding suggested that LCCL should be further investigated to develop its complementary therapeutic effect on T2DM.

Efficacy of Meal Replacement Products on Weight and Glycolipid Metabolism Management: A 90-Day Randomized Controlled Trial in Adults with Obesity

Background: The global obesity issue is growing increasingly serious, impacting personal health, economic development, and the sustainability of medical systems. There is an urgent need for effective weight loss strategies that can be widely implemented. This study conducted a 90-day randomized controlled trial to assess the impact of meal replacement products on weight management and glycolipid metabolism in adults with obesity. Methods: Adults with obesity meeting the inclusion and exclusion criteria were divided into three groups: the meal replacement group (n = 19), the diet control group (n = 19), and the normal diet group (n = 22). The meal replacement group used specially formulated meal replacement products for dinner, and the diet control group reduced the intake of staple food at lunch, both controlling daily energy intake between 1200 kcal and 1300 kcal, while the normal diet group maintained their regular dietary habits. Relevant indicators were measured at baseline and after 45 and 90 days of intervention. Results: The results showed that both the meal replacement group and the diet control group experienced significant decreases in weight, BMI, and body fat percentage, with the meal replacement group showing a more pronounced weight loss effect. The weight loss of the meal replacement group at 45 and 90 days was 4.44 ± 1.84 kg and 7.38 ± 3.24 kg, the diet control group was 2.62 ± 2.28 kg and 4.08 ± 2.94 kg, and the normal diet group was 0.66 ± 1.73 kg and 0.97 ± 2.02 kg. The decrease in BMI at 45 and 90 days for the meal replacement group was 1.08 ± 0.78 kg/m2 and 2.17 ± 1.57 kg/m2, for the diet control group was 0.82 ± 0.80 kg/m2 and 1.39 ± 1.16 kg/m2, and for the normal diet group was 0.19 ± 0.71 kg/m2 and 0.21 ± 0.96 kg/m2. The decrease in body fat percentage at 45 and 90 days for the meal replacement group was 1.76 ± 0.68% and 3.67 ± 2.62%, for the diet control group was 1.02 ± 1.11% and 1.52 ± 1.79%, and for the normal diet group was 0.81 ± 1.09% and 0.53 ± 0.93%. In addition, the decrease in BMI and body fat percentage in the meal replacement group was also significantly higher than in the other two groups. In terms of metabolic indicators, there were no significant differences in the changes of blood pressure, blood lipids, blood sugar, and ALT levels among the three groups during the intervention period. Conclusions: In summary, the results indicate that meal replacement products can significantly reduce weight and body fat percentage without affecting metabolic health.