Lipid- and gut microbiota-modulating effects of graphene oxide nanoparticles in high-fat diet-induced hyperlipidemic mice.
Ontology highlight
ABSTRACT:
SUBMITTER: Li J
PROVIDER: S-EPMC9085910 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Lipid- and gut microbiota-modulating effects of graphene oxide nanoparticles in high-fat diet-induced hyperlipidemic mice.
Li Juan J Yang Shengmei S Yu Jiaqi J Cui Rongli R Liu Ru R Lei Runhong R Chang Yanan Y Geng Huan H Qin Yanxia Y Gu Weihong W Xia Shibo S Chen Kui K Kong Jianglong J Chen Guogang G Wu Chongming C Xing Gengmei G
RSC advances 20180906 55
Graphene oxide (GO) suspensions can act as a good dispersant and drug delivery system for effective dispersion and drug sustained release. In this study, we investigated the impact of GO on blood/liver lipids and gut microbiota structure in high-fat diet (HFD)-induced hyperlipidemic mice. Oral administration of GO for 28 days remarkably decreased the lipid levels in blood and liver<i>.</i> GO did not decrease the total number of gut bacteria but increased the relative abundance of short-chain fa ...[more]
Similar Datasets
Project description:The objective of this study was to investigate the effects of simvastatin (SIM) on lipid metabolism disorders and gut microbiota in high-fat diet-induced hyperlipidemic rats. The obtained results revealed that feeding rats with SIM (20 mg/kg/day) significantly decreased serum lipid level and inhibited hepatic lipid accumulation and steatosis. Histological analysis further indicated that SIM reduced lipid deposition in adipocytes and hepatocytes in comparison with that of the HFD group. The underlying mechanisms of SIM administration against HFD-induced hyperlipidemia were also studied by UPLC-Q-TOF/MS-based liver metabonomics coupled with pathway analysis. Metabolic pathway enrichment analysis of liver metabolites with significant difference in abundance indicated that fatty acids metabolism and amino acid metabolism were the main metabolic pathways altered by SIM administration. Meanwhile, operational taxonomic units (OTUs) analysis revealed that oral administration of SIM altered the composition of gut microbiota, including Ruminococcaceae (OTU960) and Lactobacillus (OTU152), and so on. Furthermore, SIM treatment also regulated the mRNA levels of the genes involved in lipid and cholesterol metabolism. Immunohistochemistry (IHC) analysis of the liver-related proteins (CD36, CYP7A1 and SREBP-1C) showed that oral administration of SIM could regulate the levels of the protein expression related to hepatic lipid metabolism.
| S-EPMC7201051 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to explore the potential mechanisms of the lipid-regulating effects and the effect on modulating the gut microbiota of hawthorn leaf flavonoids (HLF) in the high-fat diet-induced hyperlipidemic rats.MethodsThe hypolipidemic effect of HLF was investigated in the high-fat diet-induced hyperlipidemic rats. The action targets of HLF in the treatment of hyperlipidemia were predicted by network pharmacology and KEGG enrichment bubble diagram, which were verified by the test of western blotting. Meanwhile, we used 16S rRNA sequencing to evaluate the effects of HLF on the microbes.ResultsThe results of animal experiments showed that HLF could reduce the body weight and regulate the levels of serum lipid in high-fat diet (HFD) rats. Meanwhile, for the related targets of cholesterol metabolism, HLF could significantly upregulate the expression of LDLR, NR1H3, and ABCG5/ABCG8; reduce the expression of PCSK9; and increase the level of CYP7A1 in the intestinal tissue, whereas cholesterol biosynthetic protein expressions including HMGCR and SCAP were lowered by HLF. In addition, HLF increased the activities of plasma SOD, CAT, and GSH-Px and decreased the levels of Casp 1, NLRP3, IL-1β, IL-18, and TNF-α, improving the degree of hepatocyte steatosis and inflammatory infiltration of rats. Notably, HLF significantly regulated the relative abundance of major bacteria such as g_Lactobacillus, g_Anaerostipes, g_[Eubacterium]_hallii_group, g_Fusicatenibacter, g_Akkermansia, and g_Collinsella. Synchronously, we found that HLF could regulate the disorder of plasma HEPC and TFR levels caused by HFD.ConclusionThis study demonstrates that HLF can regulate metabolic hyperlipidemia syndromes and modulate the relative abundance of major bacteria, which illustrated that it might be associated with the modulation of gut microbiota composition and metabolites.
| S-EPMC9681556 | biostudies-literature
Project description:Obesity has caused serious health and economic problems in the world. Cordyceps guangdongensis is a high-value macrofungus with broad application potential in the food and bio-medicine industry. This current study aimed to estimate the role of C. guangdongensis lipid-lowering compound formula (CGLC) in regulating fat and lipid accumulation, gut microbiota balance, short-chain fatty acid (SCFA) contents, and expression levels of genes involved in fat and lipid metabolism in high-fat diet (HFD) mice. The results showed that CGLC intervention markedly reduced body weights and fat accumulation in HFD mice, improved glucose tolerance and blood lipid levels, and decreased lipid droplet accumulation and fat vacuole levels in the liver. CGLC decreased the ratio of Firmicutes and Bacteroidetes and increased the relative abundances of Bacteroides (B. acidifaciens) and Bifidobacterium (B. pseudolongum). In addition, CGLC treatment significantly promoted the production of SCFAs and regulated the relative expression levels of genes involved in fat and lipid metabolism in liver. Association analysis showed that several species of Bacteroides and most of SCFAs were significantly associated with serum lipid indicators. These results suggested that CGLC is a novel candidate formulation for treating obesity and non-alcohol fatty liver by regulating gut microbiota, SCFAs, and genes involved in fat and lipid metabolism.
| S-EPMC9667106 | biostudies-literature
Project description:Naringenin (NAR) possesses various pharmacological activities including antioxidant, anti-inflammatory, and hepatoprotective effects. However, its therapeutic efficacy is limited by its hydrophobic and crystalline nature. This study aimed to investigate the therapeutic potential and molecular mechanisms of NAR efficiently loaded into cationic nanoparticles (NP-NAR) for treating metabolic dysfunction-associated steatotic liver disease (MASLD) in a mouse model. The results demonstrated that NP-NAR effectively ameliorated lipid metabolism dysbiosis, oxidative stress, insulin resistance, and inflammation in MASLD mice. Transcriptomic analysis and molecular data revealed that NP-NAR promoted fatty acid oxidation via activation of the PPAR signaling pathway, reduced hepatic lipid uptake and lipogenesis by inhibiting the expressions of key genes including CD36, ACC, and FASN. Moreover, NP-NAR modulated cholesterol metabolism by inhibiting the classical bile acid synthesis pathway. 16 S rDNA gene sequencing revealed a disbalanced gut microbiota in MASLD mice, whereas NP-NAR treatment statistically reversed the abundance changes of several intestinal bacteria at the phylum and genus levels, which partly contributed to the balance in intestinal metabolite production, including short-chain fatty acids. In conclusion, these findings suggest that NP-NAR may be a promising candidate for the treatment of obesity-associated MASLD, offering new insight into the mechanisms underlying NAR's efficacy against MASLD.
| S-EPMC11881431 | biostudies-literature
Project description:IntroductionThe gut microbiota plays an important role in the development of nonalcoholic steatohepatitis (NASH). This study investigated the preventive effect of Dendrobium officinale (DO), including whether its effect was related to the gut microbiota, intestinal permeability and liver inflammation.MethodsA NASH model was established in rats using a high-fat diet (HFD) and gavage with different doses of DO or Atorvastatin Calcium (AT) for 10 weeks. Body weight and body mass index along with liver appearance, weight, index, pathology, and biochemistry were measured to assess the preventive effects of DO on NASH rats. Changes in the gut microbiota were analyzed by 16S rRNA sequencing, and intestinal permeability and liver inflammation were determined to explore the mechanism by which DO treatment prevented NASH.ResultsPathological and biochemical indexes showed that DO was able to protect rats against HFD-induced hepatic steatosis and inflammation. Results of 16S rRNA sequencing showed that Proteobacteria, Romboutsia, Turicibacter, Lachnoclostridium, Blautia, Ruminococcus_torques_group, Sutterella, Escherichia-Shigella, Prevotella, Alistipes, and Lactobacillus_acidophilus differed significantly at the phylum, genus, and species levels. DO treatment modulated the diversity, richness, and evenness of gut microbiota, downregulated the abundance of the Gram-negative bacteria Proteobacteria, Sutterella, and Escherichia-Shigella, and reduced gut-derived lipopolysaccharide (LPS) levels. DO also restored expression of the tight junction proteins, zona occludens-1 (ZO-1), claudin-1, and occludin in the intestine and ameliorated the increased intestinal permeability caused by HFD, gut microbiota such as Turicibacter, Ruminococcus, Escherichia-Shigella, and Sutterella, and LPS. Lower intestinal permeability reduced LPS delivery to the liver, thus inhibiting TLR4 expression and nuclear factor-kappaB (NF-κB) nuclear translocation, improving liver inflammation.DiscussionThese results suggest that DO may alleviate NASH by regulating the gut microbiota, intestinal permeability, and liver inflammation.
| S-EPMC9968977 | biostudies-literature
Project description:Allicin, naturally present in the bulbs of the lily family, has anticancer, blood pressure lowering, blood fat lowering and diabetes improving effects. Recent studies have shown that allicin promotes the browning of white adipocytes and reduces the weight gain of mice induced by high-fat diet. While the gut microbiota has a strong relationship with obesity and energy metabolism, the effect of allicin on weight loss via gut microorganisms is still unclear. In this study, we treated obese mice induced by high-fat diet with allicin to determine its effects on fat deposition, blood metabolic parameters and intestinal morphology. Furthermore, we used high-throughput sequencing on a MiSeq Illumina platform to determine the gut microorganisms' species. We found that allicin significantly reduced the weight gain of obese mice by promoting lipolysis and thermogenesis, as well as blood metabolism and intestinal morphology, and suppressing hepatic lipid synthesis and transport. In addition, allicin changed the composition of the intestinal microbiota and increased the proportion of beneficial bacteria. In conclusion, our study showed that allicin improves metabolism in high-fat induced obese mice by modulating the gut microbiota. Our findings provide a theoretical basis for further elucidation of the weight loss mechanism of allicin.
| S-EPMC6949904 | biostudies-literature
Project description:Codium fragile (CF) is a functional seaweed food that has been used for its health effects, including immunostimulatory, anti-inflammatory, anti-obesity and anti-cancer activities, but the effect of CF extracts on obesity via regulation of intestinal microflora is still unknown. This study investigated anti-obesity effects of CF extracts on gut microbiota of diet-induced obese mice. C57BL/6 mice fed a high-fat (HF) diet were given CF extracts intragastrically for 12 weeks. CF extracts significantly decreased animal body weight and the size of adipocytes, while reducing serum levels of cholesterol and glucose. In addition, CF extracts significantly shifted the gut microbiota of mice by increasing the abundance of Bacteroidetes and decreasing the abundance of Verrucomicrobia species, in which the portion of beneficial bacteria (i.e., Ruminococcaceae, Lachnospiraceae and Acetatifactor) were increased. This resulted in shifting predicted intestinal metabolic pathways involved in regulating adipocytes (i.e., mevalonate metabolism), energy harvest (i.e., pyruvate fermentation and glycolysis), appetite (i.e., chorismate biosynthesis) and metabolic disorders (i.e., isoprene biosynthesis, urea metabolism, and peptidoglycan biosynthesis). In conclusion, our study showed that CF extracts ameliorate intestinal metabolism in HF-induced obese mice by modulating the gut microbiota.
| S-EPMC7353201 | biostudies-literature
Project description:BackgroundNumerous metabolic illnesses have obesity as a risk factor. The composition of the gut microbiota and endogenous metabolism are important factors in the onset and progression of obesity. Recent research indicates that cordycepin (CRD), derived from fungi, exhibits anti-inflammatory and antioxidant properties, showing potential in combating obesity. However, further investigation is required to delineate its precise impacts on endogenous metabolism and gut microbiota.MethodsIn this work, male C57BL/6J mice were used as models of obesity caused by a high-fat diet (HFD) and given CRD. Mice's colon, liver, and adipose tissues were stained with H&E. Serum metabolome analysis and 16S rRNA sequencing elucidated the effects of CRD on HFD-induced obese mice and identified potential mediators for its anti-obesity effects.ResultsCRD intervention alleviated HFD-induced intestinal inflammation, improved blood glucose levels, and reduced fat accumulation. Furthermore, CRD supplementation demonstrated the ability to modulate endogenous metabolic disorders by regulating the levels of key metabolites, including DL-2-aminooctanoic acid, inositol, and 6-deoxyfagomine. CRD influenced the abundance of important microbiota such as Parasutterella, Alloprevotella, Prevotellaceae_NK3B31_group, Alistipes, unclassified_Clostridia_vadinBB60_group, and unclassified_Muribaculaceae, ultimately leading to the modulation of endogenous metabolism and the amelioration of gut microbiota disorders.ConclusionsAccording to our research, CRD therapies show promise in regulating fat accumulation and stabilizing blood glucose levels. Furthermore, through the modulation of gut microbiota composition and key metabolites, CRD interventions have the dual capacity to prevent and ameliorate obesity.
| S-EPMC11396883 | biostudies-literature
Project description:IntroductionGestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance during pregnancy, estimated to affect approximately 20% of the whole pregnancies and is increasing in prevalence globally. However, there is still a big gap in knowledge about the association between gut microbiota associated metabolism alterations and GDM development.MethodsAll the participants accomplished the validated internet-based dietary questionnaire for Chinese and serum, fecal samples were collected. HFD, control diet or colesevelam intervention was fed to GDM mice models or Fxr-/- mice models, with or without antibiotics cocktail treatment. Fecal microbiota transplantation were used for further validation. Gut microbiota and metabolites were detected by metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Bile acids of serum, fecal samples from human and mice were analysised. Body weight, average feed intake, blood glucose, insulin levels and oral glucose tolerance test was performed among each groups. Expression levels of Fxr, Shp and Fgf15 mRNA and protein were detected by quantitative reverse transcription polymerase chain reaction and western blot, respectively.ResultsOur data indicated that high fat diet (HFD) was linked with higher prevalence of GDM, and HFD was positively associated with poor prognosis in GDM patients. Moreover, compared with normal diet (ND) group, GDM patients from HFD group performed a loss of gut microbiota diversity and enrichment of Alistipes onderdonkii, Lachnospiraceae bacterium 1_7_58FAA, and Clostridium aspaaragiforme while ruduction of Akkermansiaceae, Paraprevotell xylaniphila, and Prevotella copri. Additionally, HFD aggravated GDM in mice and gut microbiota depletion by antibiotics crippled the effect of excess fat intake. BAs profile altered in HFD GDM patients and mice models. Fecal microbiota transplantation (FMT) further confirmed that gut microbiota contributed to bile acids (BAs) metabolic dysfunction during HFD-associated GDM development. Mechanically, HFD-FMT administration activated Fxr, Shp, and Fgf15 activity, disturbed the glucose metabolism and aggravated insulin resistance but not in HFD-FMT Fxr-/- mice and ND-FMT Fxr-/- mice. Furthermore, colesevelam intervention alleviated HFD-associated GDM development, improved BAs metabolism, suppressed Fxr, Shp, and Fgf15 activity only in WT mice but not in the Fxr-/- HFD + Colesevelam group and Fxr-/- HFD group. HFD induced GDM and contributed to poor prognosis in GDM parturients through inducing gut microbial dysbiosis and metabolic alteration, especially appeared in BAs profile. Moreover, Fxr pathway participated in regulating HFD-associated gut microbiota disordered BAs metabolites and aggravating GDM in mice.DiscussionModulating gut microbiota and BAs metabolites could be a potential therapeutic strategy in the prevention and treatment of HFD-associated GDM.
| S-EPMC11810896 | biostudies-literature
Project description:Dysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota influences hepatic lipid metabolism has not been elucidated. Here, a gut microbiota depletion mouse model was constructed with an antibiotics cocktail (Abx) to study the mechanism through which intestinal microbiota regulates hepatic lipid metabolism in high-fat diet (HFD)-fed mice. Our results showed that the Abx treatment effectively eradicated the gut microbiota in these mice. Microbiota depletion reduced the body weight and fat deposition both in white adipose tissue and liver. In addition, microbiota depletion reduced serum levels of glucose, total cholesterol (TC), low-density lipoproteins (LDL), insulin, and leptin in HFD-fed mice. Importantly, the depletion of gut microbiota in HFD-fed mice inhibited excessive hepatic lipid accumulation. Mechanistically, RNA-seq results revealed that gut microbiota depletion changed the expression of hepatic genes involved in cholesterol and fatty acid metabolism, such as Cd36, Mogat1, Cyp39a1, Abcc3, and Gpat3. Moreover, gut microbiota depletion reduced the abundance of bacteria associated with abnormal metabolism and inflammation, including Lachnospiraceae, Coriobacteriaceae_UCG-002, Enterorhabdus, Faecalibaculum, and Desulfovibrio. Correlation analysis showed that there was strong association between the altered gut microbiota abundance and the serum cholesterol level. This study indicates that gut microbiota ameliorates HFD-induced hepatic lipid metabolic dysfunction, which might be associated with genes participating in cholesterol and fatty acid metabolism in the liver.
| S-EPMC9408850 | biostudies-literature