Glycolipid Metabolism Disorder Research Articles

Independent relationship between sleep apnea-specific hypoxic burden and glucolipid metabolism disorder: a cross-sectional study.

Obstructive sleep apnea (OSA) is associated with abnormal glucose and lipid metabolism. However, whether there is an independent association between Sleep Apnea-Specific Hypoxic Burden (SASHB) and glycolipid metabolism disorders in patients with OSA is unknown. We enrolled 2,173 participants with suspected OSA from January 2019 to July 2023 in this study. Polysomnographic variables, biochemical indicators, and physical measurements were collected from each participant. Multiple linear regression analyses were used to evaluate independent associations between SASHB, AHI, CT90 and glucose as well as lipid profile. Furthermore, logistic regressions were used to determine the odds ratios (ORs) for abnormal glucose and lipid metabolism across various SASHB, AHI, CT90 quartiles. The SASHB was independently associated with fasting blood glucose (FBG) (β = 0.058, P = 0.016), fasting insulin (FIN) (β = 0.073, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (β = 0.058, P = 0.011), total cholesterol (TC) (β = 0.100, P < 0.001), total triglycerides (TG) (β = 0.063, P = 0.011), low-density lipoprotein cholesterol (LDL-C) (β = 0.075, P = 0.003), apolipoprotein A-I (apoA-I) (β = 0.051, P = 0.049), apolipoprotein B (apoB) (β = 0.136, P < 0.001), apolipoprotein E (apoE) (β = 0.088, P < 0.001) after adjustments for confounding factors. Furthermore, the ORs for hyperinsulinemia across the higher SASHB quartiles were 1.527, 1.545, and 2.024 respectively, compared with the lowest quartile (P < 0.001 for a linear trend); the ORs for hyper-total cholesterolemia across the higher SASHB quartiles were 1.762, 1.998, and 2.708, compared with the lowest quartile (P < 0.001 for a linear trend) and the ORs for hyper-LDL cholesterolemia across the higher SASHB quartiles were 1.663, 1.695, and 2.316, compared with the lowest quartile (P < 0.001 for a linear trend). Notably, the ORs for hyper-triglyceridemia{1.471, 1.773, 2.099} and abnormal HOMA-IR{1.510, 1.492, 1.937} maintained a consistent trend across the SASHB quartiles. We found SASHB was independently associated with hyperinsulinemia, abnormal HOMA-IR, hyper-total cholesterolemia, hyper-triglyceridemia and hyper-LDL cholesterolemia in Chinese Han population. Further prospective studies are needed to confirm that SASHB can be used as a predictor of abnormal glycolipid metabolism disorders in patients with OSA. ChiCTR1900025714 { http://www.chictr.org.cn/ }; Prospectively registered on 6 September 2019; China.

Modulation of glycolipid metabolism in T2DM rats by Rubus irritans Focke extract: Insights from metabolic profiling and ERK/IRS-1 signaling pathway

Ethnopharmacological relevanceThe extracellular regulated protein kinase (ERK) plays a crucial role in the mitogen-activated protein kinase (MAPK) family, influencing apoptosis, proliferation, and differentiation. It connection to the insulin (INS) signaling cascade and the development of type 2 diabetes mellitus (T2DM) has been established. Rubus irritans Focke, an indispensable herb in Chinese Tibetan medicine for diabetes mellitus treatment, lacks a comprehensive understanding of its effects and pharmacological mechanisms in T2DM. Aim of the studyThis study aimed to elucidate the effects of Rubus irritans Focke extract (Rife) on a T2DM rat model, exploring its impact on glycemic and lipid metabolism, histopathological changes, and its potential targeting of the extracellular regulated protein kinase/insulin receptor substrate-1 (ERK/IRS-1) signaling pathway. Materials and methodsA T2DM rat model was induced by streptozotocin (STZ) injection (40 mg/kg) in high-fat diet-fed (HFD) male Wistar rats. Rife and metformin (Met) were administered for 4 weeks, and glycemic, lipid metabolism indices, and histopathological changes were assessed. Protein expression of ERK, IRS-1 in rat liver tissues was examined to evaluate the impact on the ERK/IRS-1 pathway. ResultsRife reducing hepatic ERK and IRS-1 protein expression in T2DM rats. Untargeted metabolomics identified 13 potential biomarkers and 4 differential metabolic pathways related to glycolipid metabolism disorders. ConclusionsRife demonstrated improved glycolipid metabolism in T2DM rats by inhibiting the ERK/IRS-1 related signaling pathway and influencing multiple metabolic pathways. This study provides valuable insights into the potential therapeutic mechanisms of Rife in the context of T2DM.

Hypoglycemic effect and the mechanism of action of a polysaccharide from sweet corncob in a high-fat diet and streptozotocin-induced diabetic mice

Type 2 diabetes mellitus (T2DM) is a metabolic disease caused by a glycolipid metabolism disorder and islet β-cell dysfunction. SCP-80-I is a biologically active water-soluble polysaccharide isolated from sweet corncob, an agricultural byproduct. The hypoglycemic effects of SCP-80-I on T2DM mice and its mechanisms were investigated in this study. SCP-80-I was found to significantly reduce blood glucose and lipid deposition levels in T2DM mice, as well as decrease serum leptin and increase adiponectin secretion. Interestingly, real time-polymerase chain reaction (RT-PCR) and Western blotting results revealed that SCP-80-I could regulate the expression of several glycolipid metabolisms and insulin secretion genes and proteins, including 5'-AMP-activated protein kinase (AMPK), carnitine palmitoyltransferase I (CPT1), and acetyl coenzyme A carboxylase (ACC) in the liver and AMPK, sirtuin 1 (Sirt1), peroxisome proliferator-activated receptorycoactivator-1 (PGC-1α), and uncoupling protein 2 (UCP2) in the pancreas. To have a hypoglycemic effect, SCP-80-I regulated glycolipid metabolism and islet cell function in the liver by regulating the AMPK/ACC/CPT1 signaling pathway and the AMPK/Sirt1/PGC-1α and AMPK/Sirt1/UCP2 signaling pathways. These findings improve our understanding of polysaccharides derived from sweet corncob and the use of SCP-80-I in the production of hypoglycemic foods.

Dietary Macleaya cordata extract supplementation reduced high-fat–induced damage of antioxidant capacity and immune function, and alleviated the disorder of glycolipid metabolism in Marsupenaeus japonicus

Dietary Macleaya cordata extract supplementation reduced high-fat–induced damage of antioxidant capacity and immune function, and alleviated the disorder of glycolipid metabolism in Marsupenaeus japonicus

The Effect of Coenzyme Q10 Supplementation on Bile Acid Metabolism: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation.

Bile acids play a crucial role in lipid absorption and the regulation of lipid, glucose, and energy homeostasis. Coenzyme Q10 (CoQ10), a lipophilic antioxidant, has been recognized for its positive effects on obesity and related glycolipid metabolic disorders. However, the relationship between CoQ10 and bile acids has not yet been evaluated. This study assesses the impact of CoQ10 treatment on bile acid metabolism in mice on a high-fat diet using Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry. CoQ10 reverses the reduction in serum and colonic total bile acid levels and alters the bile acid profile in mice that are caused by a high-fat diet. Seventeen potential targets of CoQ10 in bile acid metabolism are identified by network pharmacology, with six being central to the mechanism. Molecular docking shows a high binding affinity of CoQ10 to five of these key targets. Further analyses indicate that farnesoid X (FXR) receptor and Takeda G-protein coupled receptor 5 (TGR5) may be crucial targets for CoQ10 to regulate bile acid metabolism and exert beneficial effects. This study sheds light on the impact of CoQ10 in bile acids metabolism and offers a new perspective on the application of CoQ10 in metabolic health.

Exploration of Polysaccharides from Phyllanthus emblica: Isolation, Identification, and Evaluation of Antioxidant and Anti-Glycolipid Metabolism Disorder Activities.

Phyllanthus emblica is a natural medicinal herb with diverse bioactivities. Certain extracts from this herb have been confirmed to possess anti-glycolipid metabolic disorder activity. To further develop its utility value and explore its potential in combating glycolipid metabolic disorders, we designed a series of experiments to investigate the structure, antioxidant activity, and anti-glycolipid metabolic disorder activity of Phyllanthus emblica polysaccharides. In this study, we extracted and purified polysaccharides from Phyllanthus emblica and thoroughly analyzed their structure using various techniques, including NMR, methylation analysis, and surface-enhanced Raman spectroscopy. We investigated the hypolipidemic and anti-glycolipid metabolism disorder activity of Phyllanthus emblica polysaccharides for the first time utilizing oleic acid (OA) and advanced glycation end products (AGEs) as inducers. Additionally, the antioxidant activity of Phyllanthus emblica polysaccharides was assessed in vitro. These findings lay the groundwork for future investigations into the potential application of Phyllanthus emblica polysaccharides as an intervention for preventing and treating diabetes.

Metabolomics of Mice with Type 2 Diabetes and Nonalcoholic Fatty Liver Treated by Acupuncture.

To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics. Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD. After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress. Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism.

Dietary fat supplementation relieves cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis in pigs.

Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation. Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation. Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.

The effect of different treatment strategies on glycolipid metabolism disorders and cardiovascular events in primary aldosteronism.

Recent studies have explored the association between primary aldosteronism and cardiovascular disease incidence. The association between specific primary aldosteronism treatments and differential improvement in cardiovascular event rates is yet to be established. This study was designed to compare the relative effects of spironolactone therapy and surgical intervention on cardiovascular outcomes among primary aldosteronism patients. This retrospective observational study included 853 primary aldosteronism patients from the First Affiliated Hospital of China Medical University between 2014 and 2022. Patients who had completed abdominal computed tomography (CT) examinations with similar metabolic characteristics and 6-month follow-up analyses were included in this study. These patients were separated into a surgical treatment group (n = 33) and a spironolactone treatment group (n = 51). Demographic data, biochemical analysis results, liver/spleen (L/S) X-ray attenuation ratio, hospitalization frequency, and cardiovascular events were compared between the two groups. The spironolactone group demonstrated significantly improved metabolic characteristics compared to the surgical group, shown by lower BMI, blood pressure, total cholesterol (TC), insulin resistance index (IRI), and reduced non-alcoholic fatty liver disease prevalence. Metabolic parameters did not differ significantly within the surgical treatment group when comparing pre- and postoperative values. The incidence of cardiovascular events was lower in the spironolactone group compared to the surgery group (23/33 vs. 20/51, P < 0.001) despite higher hospitalization rates(37/31 vs. 61/53, P < 0.001). In patients with primary aldosteronism, spironolactone treatment is more effective than surgical intervention in remediating abnormal lipid and glucose metabolism while improving cardiovascular outcomes. Chinese clinical trial registry registration number: ChiCTR2300074574.

Mechanisms of Dangua Fang in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.

To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics. Sprague-Dawley rats with normal glucose levels were randomly divided into three groups, including a conventional diet control group (Group A), high-fat-high-sugar diet model group (Group B), and DGR group (Group C, high-fat-high-sugar diet containing 20.5 g DGR). After 10 weeks of intervention, the fasting blood glucose (FBG), 2 h blood glucose [PBG; using the oral glucose tolerance test (OGTT)], hemoglobin A1c (HbA1c), plasma total cholesterol (TC), and triglycerides (TG) were tested, and the livers of rats were removed to calculate the liver index. Then, hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis followed by database search and bioinformatics analysis. Finally, cell experiments were used to verify the results of phosphoproteomics. Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4 (MAP4k4) and phosphorylated adducin 1 (ADD1) were detected using western blotting. DGR effectively reduced PBG, TG, and the liver index (P < 0.05), and significantly decreased HbA1c, TC, and hepatic portal TG (P < 0.01), showed significant hematoxylin and eosin (HE) staining, red oil O staining, and Masson staining of liver tissue. The total spectrum was 805 334, matched spectrum was 260 471, accounting for accounting 32.3%, peptides were 19 995, modified peptides were 14 671, identified proteins were 4601, quantifiable proteins were 4417, identified sites were 15 749, and quantified sites were 14659. Based on the threshold of expression fold change ( > 1.2), DGR up-regulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins, and down-regulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins, which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism. Therefore, DGR improved biological tissue processes, including information storage and processing, cellular processes and signaling, and metabolism. The metabolic functions regulated by DGR mainly include energy production and conversion, carbohydrate transport and metabolism, lipid transport and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism. In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies. DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders, thereby regulating glycolipid metabolism through a multi-target and multi-method process.

Association Between rs2278426 Polymorphism of the ANGPTL8 Gene and Polycystic Ovary Syndrome.

To study the relationship between the single nucleotide polymorphism (SNP) rs2278426 in the angiopoietin-like protein 8 gene (ANGPTL8) and polycystic ovary syndrome (PCOS). A total of 122 patients with PCOS and 108 controls were recruited for comparison of glucose, lipid, insulin, sex hormone, and ANGPTL8 levels. Polymerase chain reaction (PCR) and gene sequencing were performed for comparison of the frequency of the CC, CT, and TT rs2278426 genotypes and the rs2278426 allele distributions between the PCOS and control groups and between the obese and non-obese subgroups of the PCOS and control groups. The frequency of the T allele was significantly higher in the PCOS group than that in the controls (P = 0.037). In the dominant genetic model, the proportion of the CT+TT genotype in the PCOS group was significantly higher than that in the controls (P = 0.047). Subgroup analysis demonstrated that the T allele proportion was significantly higher in obese PCOS group than obese control group (P = 0.027). PCOS with the CT+TT genotype had significantly higher body mass index (BMI; P = 0.001), triglyceride (TG; P = 0.005), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.035), testosterone (P = 0.041), and ANGPTL8 (P = 0.037) levels and significantly lower high-density lipoprotein (HDL) levels (P = 0.025) than PCOS with the CC genotype. Obese PCOS group with the CT+TT genotype had significantly higher TG (P = 0.015), luteinizing hormone (LH; P = 0.030), fasting insulin (FINS; P = 0.039), HOMA-IR (P = 0.018), and ANGPTL8 (P = 0.049) levels than obese PCOS group with the CC genotype. Polymorphisms of rs2278426 may induce glycolipid metabolic disorders by affecting ANGPTL8 levels and functions in Han Chinese females with obesity from the Shandong region, increasing the risk of PCOS in this population.

Alterations of intestinal mucosal barrier, cecal microbiota diversity, composition, and metabolites of yellow-feathered broilers under chronic corticosterone-induced stress: a possible mechanism underlying the anti-growth performance and glycolipid metabolism disorder.

The study aimed to determine the influence of altered intestinal mucosal barrier, cecum flora community, and metabolites on anti-growth performance, glycolipid metabolism disorders of chronic corticosterone (CORT)-induced stress (CCIS) broilers. Compared with control (CON) broilers, in CCIS broilers: (i) anti-growth performance, glycolipid metabolism disorder, and impaired intestinal immune barrier and physical barrier function were observed. (ii) From phylum to genus level, the abundances of Firmicutes and Faecalibacterium were decreased; whereas, the abundances of Proteobacteria, RuminococcaceaeUCG-005, and Escherichia coli (Shigella) were increased. (iii) Differential metabolites in cecum were mainly enriched in steroid hormone biosynthesis and tyrosine metabolism. (iv) Body weight (BW) and total cholesterol (TC) were positively correlated with Christensenellaceae_R.7_group and Escherichia_Shigella, respectively, while downregulated Faecalibacterium and Christensenellaceae were negatively correlated with upregulated metabolites. Our findings suggest that CCIS induces anti-growth performance and glycolipid metabolism disorder by altering cecum flora and metabolites, providing a theoretical basis for efforts to eliminate the effect of chronic stress on human health and animal production.

Immune metabolic mechanisms of acupuncture in improving glycolipid metabolic disorders explored through pancreatic adipose tissue.

Pancreatic adipose tissue serves as a crucial structural basis for the development of glycolipid metabolic disorders. Understanding the mechanisms underlying pancreatic adipose tissue infiltration and regulatory strategies is essential for early intervention in glycolipid metabolic disorders. Pancreatic adipose tissue functions as a significant medium linking systemic immune metabolism, while the pancreatic vascular system emerges as a novel target for sensing pancreatic immune responses and maintaining the body's energy homeostasis, collectively participating in the development of glycolipid metabolic disorders. Acupuncture possesses potential effects in modulating the interaction between resident macrophages and adipocytes in the pancreas, leading to the reversible reduction of excessive pancreatic adipose accumulation, with its action being vascular-dependent.

Chronic intermittent hypoxia aggravated diabetic cardiomyopathy through LKB1/AMPK/Nrf2 signaling pathway.

Chronic intermittent hypoxia (CIH) may play an important role in the development of diabetic cardiomyopathy (DCM). However, the exact mechanism of CIH-induced myocardial injury in DCM remains unclear. In vivo, the db/db mice exposed to CIH were established, and in vitro, the H9C2 cells were exposed to high glucose (HG) combined with intermittent hypoxia (IH). The body weight (BW), fasting blood glucose (FBG) and food intake were measured every two weeks. The glycolipid metabolism was assessed with the oral glucose tolerance test (OGTT) and insulin resistance (IR). Cardiac function was detected by echocardiography. Cardiac pathology was detected by HE staining, Masson staining, and transmission electron microscopy. The level of reactive oxygen species (ROS) in myocardial tissue was detected by dihydroethidium (DHE). The apoptosis was detected by TUNEL staining. The cell viability, ROS, and the mitochondrial membrane potential were detected by the cell counting kit-8 (CCK-8) assay and related kits. Western blotting was used to analyze the liver kinase B1/AMP-activated protein kinase/ nuclear factor-erythroid 2-related factor 2 (LKB1/AMPK/Nrf2) signaling pathway. CIH exposure accelerated glycolipid metabolism disorders and cardiac injury, and increased the level of cardiac oxidative stress and the number of positive apoptotic cells in db/db mice. IH and HG decreased the cell viability and the level of mitochondrial membrane potential, and increased ROS expression in H9C2 cells. These findings indicate that CIH exposure promotes glycolipid metabolism disorders and myocardial apoptosis, aggravating myocardial injury via the LKB1/AMPK/Nrf2 pathway in vitro and in vivo.

Living in a dynamic environment: The effects of multi-ways temperature variation on embryo and newborn juveniles of a shallow-water octopus (Amphioctopus fangsiao)

Shallow waters are characterized by fluctuating environmental conditions, modulating marine life cycles and biological phenomena. Multiple variations in water temperature could affect eggs and embryos during spawning events of many marine invertebrate species, yet most of the findings on embryonic development in invertebrates come from experiments based on the constant temperature. In this study, to examine the effects of temperature variation on octopus embryos, Amphioctopus fangsiao, a common shallow-water octopus along the coast of China, was exposed to the constant temperature (18 °C, in situ temperature of the seawater in Lianyungang), ramping temperatures (from 18 to 24 °C), diel oscillating temperatures (18 °C and 20 °C for 12 h each day), and acute increasing temperatures (the temperature increased sharply from 18 °C to 24 °C at embryonic development stage XIX) for 47 days (from embryogenesis to settlement). The results demonstrated that the temperature variations accelerated the development time of A. fangsiao embryos. Temperature fluctuations could cause embryonic oxidative damage and disorder of glycolipid metabolism, thereby affecting the growth performance of embryos and the survival rate of hatchings. Through transcriptome sequencing, the mechanistic adaption of the embryo to environmental temperature variations was revealed. The pathways involved in the TCA cycle, DNA replication and repair, protein synthesis, cell signaling, and nervous system damage repair were significantly enriched, indicating that the embryo could improve heat tolerance to thermal stress by regulating gene expression. Moreover, acute warming temperatures posed the most detrimental effects on A. fangsiao embryos, which could cause embryos to hatch prematurely from the vegetal pole, further reducing the survival of hatchings. Meanwhile, the diel oscillating temperature was observed to affect the normal morphology of the embryo, resulting in embryo deformities. Thus, the constant temperature is critical for balanced growth and defense status in octopuses by maintaining metabolism homeostasis. For the first time, this study evaluates the effects of multiple temperature fluctuations on embryos of A. fangsiao, providing new insights into the physiological changes and molecular responses of cephalopod embryos following dynamic temperature stress.

Proanthocyanidins isolated from lotus seed skin mitigate glycolipid metabolism disorder through the p38/Nrf2/NF-κB signaling pathway.

Lotus seed skin extract is rich in flavonoids, making it a promising candidate for developing health products. In a previous study, we found that proanthocyanidins from lotus seed skin, particularly proanthocyanidin B1 (PB1), can indirectly activate the Nrf2 signaling pathway, exerting an antioxidant effect. In this study, we isolate proanthocyanidins from lotus seed skin (PLS) using ethanol extraction and RP-HPLC identification, and investigate its effects on glycolipid metabolism both in vivo and in vitro. Our results demonstrate that PLS reduces body weight in high-fat diet (HFD) mice by decreasing feed efficiency. PLS also normalizes serum glucose, insulin secretion, glycosylated hemoglobin (HbA1c), and intraperitoneal glucose tolerance (IPGTT). Furthermore, PLS significantly improves blood lipid parameters and inhibits the expressions of six proinflammatory factors, including IL-1α, IL-1β, IL-3, IL-6, IFN-γ and TNF-α in HFD mice. Additionally, analysis of fresh liver tissues reveals that PLS and PB1 induce the expressions of antioxidant proteins such as HO-1 and NQO1 by activating the p38-Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway. In conclusion, proanthocyanidins from lotus seed skin regulate glycolipid metabolism disorders by targeting the p38/Nrf2/NF-κB signaling pathway. Our study offers a new approach for the high-value comprehensive utilization of lotus seed skin by-products and precise dietary intervention for metabolic syndrome.

Mechanisms of Action of Potentilla discolor Bunge in Type 2 Diabetes Mellitus Based on Network Pharmacology and Experimental Verification in Drosophila.

Type 2 diabetes mellitus (T2DM) is associated with reduced insulin uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been used to treat T2DM; however, the fundamental biological mechanisms remain unclear. This study aimed to understand the active ingredients, potential targets, and underlying mechanisms through which PDB treats T2DM. Components and action targets were predicted using network pharmacology and molecular docking analyses. PDB extracts were prepared and validated through pharmacological intervention in a Cg>InRK1409A diabetes Drosophila model. Network pharmacology and molecular docking analyses were used to identify the key components and core targets of PDB in the treatment of T2DM, which were subsequently verified in animal experiments. Network pharmacology analysis revealed five effective compounds made up of 107 T2DM-related therapeutic targets and seven protein-protein interaction network core molecules. Molecular docking results showed that quercetin has a strong preference for interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to tumor necrosis factor and AKT1; β-sitosterol demonstrated pronounced binding to Caspase-3 (CASP3). High-performance liquid chromatography data quantified quercetin, kaempferol, and β-sitosterol at proportions of 0.030%, 0.025%, and 0.076%, respectively. The animal experiments revealed that PDB had no effect on the development, viability, or fertility of Drosophila and it ameliorated glycolipid metabolism disorders in the diabetes Cg>InRK1409A fly. Furthermore, PDB improved the body size and weight of Drosophila, suggesting its potential to alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM. Our findings suggest that PDB ameliorates diabetes metabolism disorders in the fly model by enhancing Akt activity and suppressing CASP3 expression. This will facilitate the development of key drug targets and a potential therapeutic strategy for the clinical treatment of T2DM and related metabolic diseases.

Extract of Gardenia jasminoides Ellis Attenuates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats by Targeting Gut Microbiota and TLR4/Myd88/NF-κB Pathway.

Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

Threats of nano/microplastics to reproduction and offspring: Potential mechanisms and perspectives

Due to the ubiquitous occurrence in the aquatic environment and terrestrial ecosystem and underlying eco-environmental risks, nano/microplastics (NPs/MPs) have sparked great public concerns. The purpose of this work is aimed to summarize the harmful influence of NPs/MPs on reproduction and offspring health and further explore the potential mechanisms of action, thereby facilitating the more comprehensive understanding of NPs/MPs features. Literature search databases included EMBASE, Web of Science, and PubMed. The study selection and data extraction were implemented according to the inclusion criteria. NPs/MPs could accumulate and trigger reproductive toxic responses and thereafter generate deleterious effects on the offspring health. Accordingly, the reproductive toxicity of NPs/MPs was characterized as the sperm deformity, decline in sperm count and motility, follicular growth tardiness, ovarian fibrosis, granulosa cell death, disorder of reproductive hormone secretion, as well as the fetal growth restriction, glycolipid metabolism disorder, and inflammatory responses of the next generation. Additionally, mechanism research revealed that NPs/MPs exposure brought about inflammatory responses and oxidative stress and thereafter, destroyed the blood-testis barrier (BTB) integrity, motivated spermatogenic cell apoptosis by activating the JNK and p38/MAPK-Nrf2/NF-κB pathways, and induced ovarian granulosa cell pyroptosis and apoptosis and subsequent ovarian fibrosis via the Wnt/β-Catenin and NLRP3/Caspase-1 pathways. Nevertheless, this work also highlighted the imperative requirements for scientific and systematic risk assessments of NPs/MPs, so as to identify the feasible risk mitigation strategies.

Methylparaben induces hepatic glycolipid metabolism disorder by activating the IRE1α-XBP1 signaling pathway in male mice

Methylparaben (MP), a preservative widely used in daily supplies, exists in both the environment and the human body. However, the potential health risks posed by MP remain unclear. This study aimed to unravel the mechanisms by which MP disrupts glucose and lipid homeostasis. For this, we administered MP to mice and observed changes in glucose and lipid metabolism. MP exposure led to hyperglycemia, hyperlipidemia, visceral organ injury, and hepatic lipid accumulation. RNA sequencing results from mice livers indicated a close association between MP exposure and endoplasmic reticulum (ER) stress, inflammatory response, and glucose and lipid homeostasis. Western blotting and quantitative reverse transcription–polymerase chain reaction revealed that MP activated ER stress, particularly the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) pathway, which further promoted the activation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. The activation of these pathways phosphorylated insulin receptor substrate-1 (IRS1) (ser 307), resulting in decreased phosphorylation of protein kinase B (Akt) (ser 473), leading to insulin resistance. Additionally, MP exposure promoted lipogenesis through ER stress. To explore potential remedies, we administered the ER stress inhibitor 4-phenylbutyric acid (4-PBA) and the IRE1α-XBP1 pathway inhibitor toyocamycin to mice, both of which protected against metabolic disorders and organ injury caused by MP. These findings suggest that MP induces disruptions in glucose and lipid metabolism through ER stress, primarily through the IRE1α-XBP1 pathway.