-
Food & Function Jun 2024The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that - and -derived fucoidans have type I and type... (Comparative Study)
Comparative Study
The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that - and -derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in -derived fucoidans than those of -derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both - and -derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, -derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.
Topics: Animals; Laminaria; Ascophyllum; Mice; Polysaccharides; Hypolipidemic Agents; Apolipoproteins E; Male; Mice, Inbred C57BL; Triglycerides; Cholesterol; Mice, Knockout; PPAR alpha; Hyperlipidemias; Plant Extracts; Liver; Humans; Edible Seaweeds
PubMed: 38738998
DOI: 10.1039/d3fo05521c -
Journal of Advanced Research May 2024Depression is a debilitating and poorly understood mental disorder. There is an urgency to explore new potential biological mechanisms of depression and the gut...
INTRODUCTION
Depression is a debilitating and poorly understood mental disorder. There is an urgency to explore new potential biological mechanisms of depression and the gut microbiota is a promising research area.
OBJECTIVES
Our study was aim to understand regional heterogeneity and potential molecular mechanisms underlying depression induced by dysbiosis of mucus-associated microbiota.
METHODS
Here, we only selected female macaques because they are more likely to form a natural social hierarchy in a harem-like environment. Because high-ranking macaques rarely displayed depressive-like behaviors, we selected seven monkeys from high-ranking individuals as control group (HC) and the same number of low-ranking ones as depressive-like group (DL), which displayed significant depressive-like behaviors. Then, we collected mucus from the duodenum, jejunum, ileum, cecum and colon of DL and HC monkeys for shotgun metagenomic sequencing, to profile the biogeography of mucus-associated microbiota along duodenum to colon.
RESULTS
Compared with HC, DL macaques displayed noticeable depressive-like behaviors such as longer duration of huddle and sit alone behaviors (negative emotion behaviors), and fewer duration of locomotion, amicable and ingestion activities (positive emotion behaviors). Moreover, the alpha diversity index (Chao) could predict aforementioned depressive-like behaviors along duodenum to colon. Further, we identified that genus Pseudomonas was consistently decreased in DL group throughout the entire intestinal tract except for the jejunum. Specifically, there were 10, 18 and 28 decreased Pseudomonas spp. identified in ileum, cecum and colon, respectively. Moreover, a bacterial module mainly composed of Pseudomonas spp. was positively associated with three positive emotion behaviors. Functionally, Pseudomonaswas mainly involved in microbiota derived lipid metabolisms such as PPAR signaling pathway, cholesterol metabolism, and fat digestion and absorption.
CONCLUSION
Different regions of intestinal mucus-associated microbiota revealed that depletion of genus Pseudomonas is associated with depressive-like behaviors in female macaques, which might induce depressive phenotypes through regulating lipid metabolism.
PubMed: 38735389
DOI: 10.1016/j.jare.2024.05.013 -
Toxicology Letters Jun 2024The activation of pregnane X receptor (PXR) or peroxisome proliferator-activated receptor α (PPARα) can induce liver enlargement. Recently, we reported that PXR or...
The activation of pregnane X receptor (PXR) or peroxisome proliferator-activated receptor α (PPARα) can induce liver enlargement. Recently, we reported that PXR or PPARα activation-induced hepatomegaly depends on yes-associated protein (YAP) signaling and is characterized by hepatocyte hypertrophy around the central vein area and hepatocyte proliferation around the portal vein area. However, it remains unclear whether PXR or PPARα activation-induced hepatomegaly can be reversed after the withdrawal of their agonists. In this study, we investigated the regression of enlarged liver to normal size following the withdrawal of PCN or WY-14643 (typical agonists of mouse PXR or PPARα) in C57BL/6 mice. The immunohistochemistry analysis of CTNNB1 and KI67 showed a reversal of hepatocyte size and a decrease in hepatocyte proliferation after the withdrawal of agonists. In details, the expression of PXR or PPARα downstream proteins (CYP3A11, CYP2B10, ACOX1, and CYP4A) and the expression of proliferation-related proteins (CCNA1, CCND1, and PCNA) returned to the normal levels. Furthermore, YAP and its downstream proteins (CTGF, CYR61, and ANKRD1) also restored to the normal states, which was consistent with the change in liver size. These findings demonstrate the reversibility of PXR or PPARα activation-induced hepatomegaly and provide new data for the safety of PXR and PPARα as drug targets.
Topics: Animals; PPAR alpha; Hepatomegaly; Pregnane X Receptor; YAP-Signaling Proteins; Mice, Inbred C57BL; Pyrimidines; Hepatocytes; Male; Liver; Cell Proliferation; beta Catenin; Signal Transduction; Adaptor Proteins, Signal Transducing; Cell Cycle Proteins; Cytochrome P-450 CYP4A; Cytochrome P450 Family 4; Mice; Phosphoproteins; Ki-67 Antigen; Membrane Proteins; Steroid Hydroxylases; Cytochrome P450 Family 2; Cytochrome P-450 CYP3A; Aryl Hydrocarbon Hydroxylases
PubMed: 38734220
DOI: 10.1016/j.toxlet.2024.05.006 -
Translational Research : the Journal of... Sep 2024Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms...
Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to β-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.
Topics: Animals; PPAR alpha; Protein Glutamine gamma Glutamyltransferase 2; Lipid Metabolism; Male; Doxorubicin; Fibroins; Signal Transduction; Kidney Diseases; Peptides; Rats; Nerve Tissue Proteins; Rats, Sprague-Dawley
PubMed: 38734063
DOI: 10.1016/j.trsl.2024.05.006 -
Nutrients Apr 2024Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether...
Prenatal Choline Supplementation Improves Glucose Tolerance and Reduces Liver Fat Accumulation in Mouse Offspring Exposed to Ethanol during the Prenatal and Postnatal Periods.
Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether postnatal AE exacerbates metabolic deterioration resulting from prenatal AE. Choline is a semi-essential nutrient that has been demonstrated to mitigate the cognitive impairment of prenatal AE. This study investigated how maternal choline supplementation (CS) may modify the metabolic health of offspring with prenatal and postnatal AE (AE/AE). C57BL/6J female mice were fed either a Lieber-DeCarli diet with 1.4% ethanol between embryonic day (E) 9.5 and E17.5 or a control diet. Choline was supplemented with 4 × concentrations versus the control throughout pregnancy. At postnatal week 7, offspring mice were exposed to 1.4% ethanol for females and 3.9% ethanol for males for 4 weeks. AE/AE increased hepatic triglyceride accumulation in male offspring only, which was normalized by prenatal CS. Prenatal CS also improved glucose tolerance compared to AE/AE animals. AE/AE suppressed hepatic gene expression of peroxisome proliferator activated receptor alpha () and low-density lipoprotein receptor (), which regulate fatty acid catabolism and cholesterol reuptake, respectively, in male offspring. However, these changes were not rectified by prenatal CS. In conclusion, AE/AE led to an increased risk of steatosis and was partially prevented by prenatal CS in male mice.
Topics: Animals; Female; Pregnancy; Choline; Ethanol; Male; Dietary Supplements; Liver; Prenatal Exposure Delayed Effects; Mice, Inbred C57BL; Mice; Fatty Liver; Triglycerides; PPAR alpha; Receptors, LDL; Glucose Intolerance; Lipid Metabolism
PubMed: 38732511
DOI: 10.3390/nu16091264 -
Nutrients Apr 2024Isoeugenol (IEG), a natural component of clove oil, possesses antioxidant, anti-inflammatory, and antibacterial properties. However, the effects of IEG on adipogenesis...
Isoeugenol (IEG), a natural component of clove oil, possesses antioxidant, anti-inflammatory, and antibacterial properties. However, the effects of IEG on adipogenesis have not yet been elucidated. Here, we showed that IEG blocks adipogenesis in 3T3-L1 cells at an early stage. IEG inhibits lipid accumulation in adipocytes in a concentration-dependent manner and reduces the expression of mature adipocyte-related factors including PPARγ, C/EBPα, and FABP4. IEG treatment at different stages of adipogenesis showed that IEG inhibited adipocyte differentiation by suppressing the early stage, as confirmed by lipid accumulation and adipocyte-related biomarkers. The early stage stimulates growth-arrested preadipocytes to enter mitotic clonal expansion (MCE) and initiates their differentiation into adipocytes by regulating cell cycle-related factors. IEG arrested 3T3-L1 preadipocytes in the G/G phase of the cell cycle and attenuated cell cycle-related factors including cyclinD1, CDK6, CDK2, and cyclinB1 during the MCE stage. Furthermore, IEG suppresses reactive oxygen species (ROS) production during MCE and inhibits ROS-related antioxidant enzymes, including superoxide dismutase1 (SOD1) and catalase. The expression of cell proliferation-related biomarkers, including pAKT and pERK1/2, was attenuated by the IEG treatment of 3T3-L1 preadipocytes. These findings suggest that it is a potential therapeutic agent for the treatment of obesity.
Topics: Animals; Adipogenesis; 3T3-L1 Cells; Mice; Adipocytes; Mitosis; Eugenol; Reactive Oxygen Species; Cell Differentiation; PPAR gamma; Cell Proliferation; Fatty Acid-Binding Proteins; Lipid Metabolism; CCAAT-Enhancer-Binding Protein-alpha; Antioxidants
PubMed: 38732509
DOI: 10.3390/nu16091262 -
International Journal of Molecular... Apr 2024"" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study,...
"" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.
Topics: Mice; Plant Extracts; Animals; 3T3-L1 Cells; Hypoglycemic Agents; Adipogenesis; Adipocytes; PPAR gamma; Anti-Obesity Agents; Obesity; Glucose Transporter Type 4; CCAAT-Enhancer-Binding Protein-alpha; alpha-Glucosidases; AMP-Activated Protein Kinases; Antioxidants; Glycoside Hydrolase Inhibitors; Crassulaceae; Lipid Metabolism; Cell Differentiation
PubMed: 38732125
DOI: 10.3390/ijms25094908 -
Molecules (Basel, Switzerland) Apr 2024Carbon nanodots (CDs) are commonly found in food products and have attracted significant attention from food scientists. There is a high probability of CD exposure in...
Carbon nanodots (CDs) are commonly found in food products and have attracted significant attention from food scientists. There is a high probability of CD exposure in humans, but its impacts on health are unclear. Therefore, health effects associated with CD consumption should be investigated. In this study, we attempted to create a model system of the Maillard reaction between cystine and glucose using a simple cooking approach. The CDs (CG-CDs) were isolated from cystine-glucose-based Maillard reaction products and characterized using fluorescence spectroscopy, X-ray diffractometer (XRD), and transmission electron microscope (TEM). Furthermore, human mesenchymal stem cells (hMCs) were used as a model to unravel the CDs' cytotoxic properties. The physiochemical assessment revealed that CG-CDs emit excitation-dependent fluorescence and possess a circular shape with sizes ranging from 2 to 13 nm. CG-CDs are predominantly composed of carbon, oxygen, and sulfur. The results of the cytotoxicity evaluation indicate good biocompatibility, where no severe toxicity was observed in hMCs up to 400 μg/mL. The DPPH assay demonstrated that CDs exert potent antioxidant abilities. The qPCR analysis revealed that CDs promote the downregulation of the key regulatory genes, PPARγ, C/EBPα, SREBP-1, and HMGCR, coupled with the upregulation of anti-inflammatory genes. Our findings suggested that, along with their excellent biocompatibility, CG-CDs may offer positive health outcomes by modulating critical genes involved in lipogenesis, homeostasis, and obesity pathogenesis.
Topics: Humans; Maillard Reaction; Carbon; PPAR gamma; Sterol Regulatory Element Binding Protein 1; Mesenchymal Stem Cells; CCAAT-Enhancer-Binding Protein-alpha; Quantum Dots; Down-Regulation; Gene Expression Regulation; Antioxidants; Sulfur
PubMed: 38731499
DOI: 10.3390/molecules29092008 -
Animals : An Open Access Journal From... Apr 2024Non-alcoholic fatty liver disease (NAFLD) is strongly associated with hyperlipidemia, which is closely related to high levels of sugar and fat. β-sitosterol is a...
OBJECTIVE
Non-alcoholic fatty liver disease (NAFLD) is strongly associated with hyperlipidemia, which is closely related to high levels of sugar and fat. β-sitosterol is a natural product with significant hypolipidemic and cholesterol-lowering effects. However, the underlying mechanism of its action on aquatic products is not completely understood.
METHODS
A high-fat diet (HFD)-induced NAFLD zebrafish model was successfully established, and the anti-hyperlipidemic effect and potential mechanism of β-sitosterol were studied using oil red O staining, filipin staining, and lipid metabolomics.
RESULTS
β-sitosterol significantly reduced the accumulation of triglyceride, glucose, and cholesterol in the zebrafish model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differential lipid molecules in β-sitosterol mainly regulated the lipid metabolism and signal transduction function of the zebrafish model. β-sitosterol mainly affected steroid biosynthesis and steroid hormone biosynthesis in the zebrafish model. Compared with the HFD group, the addition of 500 mg/100 g of β-sitosterol significantly inhibited the expression of and in the zebrafish model by at least 50% and 25%, respectively.
CONCLUSIONS
β-sitosterol can reduce lipid accumulation in the zebrafish model of NAFLD by regulating lipid metabolism and signal transduction and inhibiting adipogenesis and lipid storage.
PubMed: 38731293
DOI: 10.3390/ani14091289 -
ACS Chemical Neuroscience Jun 2024Aggregative α-synuclein and incurring oxidative stress are pivotal cascading events, leading to dopaminergic (DAergic) neuronal loss and contributing to clinical...
2-Butoxytetrahydrofuran, Isolated from , Attenuates Aggregative and Oxidative Properties of α-Synuclein and Alleviates Its Toxicity in a Transgenic Model of Parkinson's Disease.
Aggregative α-synuclein and incurring oxidative stress are pivotal cascading events, leading to dopaminergic (DAergic) neuronal loss and contributing to clinical manifestations of Parkinson's disease (PD). Our previous study demonstrated that 2-butoxytetrahydrofuran (2-BTHF), isolated from (), could inhibit amyloid-β aggregation and its ensuing toxicity, which leads to Alzheimer's disease. In the present study, we found that 2-BTHF also attenuated the aggregative and oxidative activities of α-synuclein and lessened its toxicity in a transgenic () PD model. Such worms treated with 100 μM of 2-BTHF showed substantial reductions in α-synuclein accumulation and DAergic neurodegeneration. Mechanistically, 2-BTHF, at this concentration, significantly decreased aggregation of monomeric α-synuclein and restored locomotion and dopamine-dependent behaviors. Molecular docking exhibited potential bindings of 2-BTHF to HSF-1 and DAF-16 transcription factors. Additionally, 2-BTHF significantly increased the mRNA transcripts of genes encoding proteins involved in proteostasis, including the molecular chaperones and , the ubiquitination/SUMOylation-related gene, and the autophagy-related genes and . Transcriptomic profiling revealed an additional mechanism of 2-BTHF in α-synuclein-expressing worms, which showed upregulation of PPAR signaling cascades that mediated fatty acid metabolism. 2-BTHF significantly restored lipid deposition, upregulated the gene, and enhanced -mediated glutathione synthesis in the PD model. Taken together, this study demonstrated that 2-BTHF could abrogate aggregative and oxidative properties of α-synuclein and attenuate its toxicity, thus providing a possible therapeutic application for the treatment of α-synuclein-induced PD.
Topics: Animals; Caenorhabditis elegans; alpha-Synuclein; Animals, Genetically Modified; Oxidative Stress; Disease Models, Animal; Furans; Holothuria; Parkinson Disease; Caenorhabditis elegans Proteins; Molecular Docking Simulation; Dopaminergic Neurons; Humans
PubMed: 38726817
DOI: 10.1021/acschemneuro.4c00008