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Turmeric, derived from Curcuma longa, and Lactobacillus paracasei, a lactic acid bacteria, have been studied for their potential antiobesity effects. To date, the antiobesity effects of turmeric fermented with L. paracasei have not been sufficiently investigated. This study was conducted via oral administration of 5% L. paracasei-fermented (FT) and unfermented turmeric (UT) in diet over 16 weeks using high-fat diet (HFD)-induced obese C57BL/6J mice. Results showed that the curcuminoid content of turmeric decreased following fermentation. Furthermore, FT significantly suppressed weight gain and liver and visceral adipose tissue weight and reduced plasma metabolic parameters in both the UT and FT experimental groups. The effects of FT were more noticeable than those of the unfermented form. Moreover, FT downregulated the expression of adipogenesis, lipogenesis, and inflammatory-related protein, but upregulated liver ß-oxidation protein SIRT 1, PPARα, and PGC-1α in perigonadal adipose tissue. Additionally, FT ameliorated insulin resistance by activating insulin receptor pathway protein expressions in visceral adipose tissues. FT also modulated gut microbiota composition, particularly in two beneficial bacteria, Akkermansia muciniphila and Desulfovibrio, as well as two short-chain fatty acid-producing bacteria: Muribaculum intestinale and Deltaproteobacteria. Our findings indicate that the modulation effect of FT may be an important pathway for its antiobesity mechanisms.
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Curcuma , Dieta Alta en Grasa , Fermentación , Microbioma Gastrointestinal , Lacticaseibacillus paracasei , Ratones Endogámicos C57BL , Obesidad , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Obesidad/metabolismo , Obesidad/microbiología , Ratones , Curcuma/química , Curcuma/metabolismo , Masculino , Lacticaseibacillus paracasei/metabolismo , Humanos , Fármacos Antiobesidad/administración & dosificación , Adipogénesis/efectos de los fármacos , Hígado/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , PPAR alfa/metabolismo , PPAR alfa/genética , Resistencia a la Insulina , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Bacterias/efectos de los fármacosRESUMEN
Obesity is a global health crisis, marked by excessive fat in tissues that function as immune organs, linked to microbiota dysregulation and adipose inflammation. Investigating the effects of Lactobacillus rhamnosus SG069 (LR069) and Lactobacillus brevis SG031 (LB031) on obesity and lipid metabolism, this research highlights adipose tissue's critical immune-metabolic role and the probiotics' potential against diet-induced obesity. Mice fed a high-fat diet were treated with either LR069 or LB031 for 12 weeks. Administration of LB031 boosted lipid metabolism, indicated by higher AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and increased the M2/M1 macrophage ratio, indicating LB031's anti-inflammatory effect. Meanwhile, LR069 administration not only led to significant weight loss by enhancing lipolysis which evidenced by increased phosphorylation of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) but also elevated Akkermansia and fecal acetic acid levels, showing the gut microbiota's pivotal role in its antiobesity effects. LR069 and LB031 exhibit distinct effects on lipid metabolism and obesity, underscoring their potential for precise interventions. This research elucidates the unique impacts of these strains on metabolic health and highlights the intricate relationship between gut microbiota and obesity, advancing our knowledge of probiotics' therapeutic potential.
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Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.
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Fármacos Antiobesidad , Curcumina , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Obesidad , Animales , Curcumina/química , Curcumina/farmacología , Curcumina/metabolismo , Ratones , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Masculino , Fármacos Antiobesidad/química , Fármacos Antiobesidad/administración & dosificación , Humanos , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/química , Termogénesis/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo/químicaRESUMEN
SCOPE: This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS AND RESULTS: Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg-1) or high (2 mg kg-1) doses of L-Glutamine daily, with 5-FU (50 mg kg-1) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa. CONCLUSIONS: These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.
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Fluorouracilo , Microbioma Gastrointestinal , Glutamina , Mucosa Intestinal , Mucositis , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Fluorouracilo/efectos adversos , Glutamina/farmacología , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Mucositis/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Ratones Endogámicos ICR , Masculino , Receptor Toll-Like 4/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Disbiosis/inducido químicamente , Disbiosis/tratamiento farmacológico , Ratones , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Antimetabolitos Antineoplásicos/efectos adversos , Hemo-Oxigenasa 1/metabolismoRESUMEN
Inflammatory bowel disease alters the gut microbiota, causes defects in mucosal barrier function, and leads to dysregulation of the immune response to microbial stimulation. This study investigated and compared the efficacy of a candidate probiotic strain, Bacillus coagulans BC198, and its heat-killed form in treating dextran sulfate sodium-induced colitis. Both live and heat-killed B. coagulans BC198 increased gut barrier-associated protein expression, reduced neutrophil and M1 macrophage infiltration of colon tissue, and corrected gut microbial dysbiosis induced by colitis. However, only live B. coagulans BC198 could alleviate the general symptoms of colitis, prevent colon shortening, and suppress inflammation and tissue damage. At the molecular level, live B. coagulans BC198 was able to inhibit Th17 cells while promoting Treg cells in mice with colitis, reduce pro-inflammatory MCP-1 production, and increase anti-inflammatory IL-10 expression in the colonic mucosa. The live form of B. coagulans BC198 functioned more effectively than the heat-killed form in ameliorating colitis by enhancing the anti-inflammatory response and promoting Treg cell accumulation in the colon.
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Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression of fibrosis-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-ß), as well as the hydroxyproline content, which decreased after treatment with FCE and TNHD. Animal experiments revealed that FCE and TNHD can reduce liver fibrosis by inhibiting cytokines that activate stellate cells and decreasing extracellular matrix (ECM) secretion. Cell experiments have shown that TNHD inhibits the MAPK/Smad signaling pathway and TGF-ß1 activation, resulting in a reduction in the expression of fibrosis-related proteins. Therefore, freshwater clam extracts, particularly TNHD, may have potential therapeutic and preventive effects for the amelioration of liver fibrosis.
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Bivalvos , Dimetilnitrosamina , Dioxolanos , Animales , Dimetilnitrosamina/toxicidad , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/genética , Bivalvos/genética , InflamaciónRESUMEN
Skeletal muscle is the largest metabolic tissue responsible for systemic glucose handling. Glucose uptake into skeletal tissue is highly dynamic and delicately regulated, in part through the controlled expression and subcellular trafficking of multiple types of glucose transporters. Although the roles of GLUT4 in skeletal muscle metabolism are well established, the physiological significance of other, seemingly redundant, glucose transporters remain incompletely understood. Nonetheless, recent studies have shed light on the roles of several glucose transporters, such as GLUT1 and GLUT10, in skeletal muscle. Mice experiments suggest that GLUT10 could be a novel player in skeletal muscle metabolism in the context of mechanical overload, which is in line with the meta-analytical results of gene expression changes after resistance exercise in humans. Herein we discuss the knowns, unknowns, and implications of these recent findings.
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Proteínas Facilitadoras del Transporte de la Glucosa , Proteínas de Transporte de Monosacáridos , Animales , Humanos , Ratones , Transporte Biológico , Glucosa/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Insulina/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Músculo Esquelético/metabolismoRESUMEN
Inflammatory bowel disease (IBD) is a chronic, nonspecific inflammation of the intestines that primarily comprises Crohn's disease and ulcerative colitis. The incidence and prevalence of IBD have been increasing globally, highlighting the significance of research and prophylactic interventions. Virofree, a mixture of various botanical extracts (including grapes, cherries, olive leaves, marigolds, green tea, and others), has shown significant potential in disease prevention. This study examined the effects of Virofree on intestinal inflammation and the gut microbiota in mice using a dextran sulfate sodium (DSS)-induced model. The mice showed no adverse reactions when administered Virofree. Virofree administration reduced the disease activity index as indicated by amelioration of DSS-induced symptoms in the mice, including weight loss, diarrhea, and rectal bleeding. Regarding the gut microbiota, Virofree intervention modulated the DSS-induced decrease in gut microbial diversity; the Virofree group showed no increase in the phyla Proteobacteria or Verrucomicrobia while displaying an increase in the genus Duncaniella, bacteria that may have protective properties. These findings suggest that Virofree may have a direct or indirect impact on the composition of the gut microbiota and that it can alleviate the imbalance of the microbiome and intestinal inflammation caused by DSS treatment.
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Benzo[a]pyrene (B[a]P) is a genotoxic polycyclic aromatic hydrocarbon that is metabolized by cytochrome P450 family 1 enzymes (CYP 1s) and can bind to DNA to form DNA adducts, leading to DNA damage and increased colorectal cancer risk. Previous studies have shown polymethoxyflavones to have a high potential for anticancer effects by regulating CYP 1s, especially nobiletin (NBT) and 5-demethylnobiletin (5-DMNB). However, the effects of NBT and 5-DMNB on B[a]P metabolism remain unclear. Therefore, this study aimed to clarify the effects of NBT and 5-DMNB on B[a]P-induced DNA damage in vitro and in vivo. In NCM460 cells, 5-DMNB and NBT appeared to reduce the metabolic conversion of B[a]P by regulating the aryl hydrocarbon receptor (AhR)/CYP 1s signaling pathway. This process protected NCM460 cells from B[a]P's cytotoxic effects by decreasing DNA damage and suppressing B[a]P diol-epoxide-DNA adduct formation. In BALB/c mice, 5-DMNB and NBT also protected against B[a]P-induced DNA damage. Altogether, these findings indicate that 5-DMNB and NBT attenuate B[a]P-induced DNA damage by modulating biotransformation, highlighting their chemopreventive potential against B[a]P-induced carcinogenesis. Therefore, 5-DMNB and NBT are promising agents for colorectal cancer chemoprevention in the future.
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Benzo(a)pireno , Neoplasias Colorrectales , Ratones , Animales , Benzo(a)pireno/toxicidad , Benzo(a)pireno/metabolismo , Xenobióticos , Daño del ADN , Aductos de ADN , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genéticaRESUMEN
The era of next-generation sequencing has increased the pace of gene discovery in the field of pediatric movement disorders. Following the identification of novel disease-causing genes, several studies have aimed to link the molecular and clinical aspects of these disorders. This perspective presents the developing stories of several childhood-onset movement disorders, including paroxysmal kinesigenic dyskinesia, myoclonus-dystonia syndrome, and other monogenic dystonias. These stories illustrate how gene discovery helps focus the research efforts of scientists trying to understand the mechanisms of disease. The genetic diagnosis of these clinical syndromes also helps clarify the associated phenotypic spectra and aids the search for additional disease-causing genes. Collectively, the findings of previous studies have led to increased recognition of the role of the cerebellum in the physiology and pathophysiology of motor control-a common theme in many pediatric movement disorders. To fully exploit the genetic information garnered in the clinical and research arenas, it is crucial that corresponding multi-omics analyses and functional studies also be performed at scale. Hopefully, these integrated efforts will provide us with a more comprehensive understanding of the genetic and neurobiological bases of movement disorders in childhood.
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Evidence shows that the dietary intake of polycyclic aromatic hydrocarbons (PAHs) from food processing induces the cellular DNA damage response and leads to the development of colorectal cancer (CRC). Therefore, protecting from cellular DNA damage might be an effective strategy in preventing CRC. Benzo[a]pyrene (B[a]P) was used as a CRC initiator in the present study. Compared with other stilbenoids, piceatannol (PIC) showed the most effective inhibition of B[a]P-induced cytochrome P450 1B1 (CYP1B1) protein expression in NCM460 normal human colon epithelial cells. PIC treatment alleviated DNA migration and enhanced the expression of DNA-repair-related proteins, including histone 2AX (H2AX), checkpoint kinase 1 (Chk1), and p53, in B[a]P-induced NCM460 cells. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) revealed that PIC exerted antioxidative effects on NCM460 cells by increasing the glutathione (GSH) content and scavenging the excess intracellular reactive oxygen species (ROS) induced by B[a]P. Furthermore, PIC suppressed B[a]P-induced CYP1B1 protein expression and stimulated miR-27b-3p expression. The upregulation of phase II detoxification enzymes, such as nicotinamide adenine dinucleotide phosphate (NADPH) and quinone oxidoreductase 1 (NQO1), and the antioxidative enzyme, heme oxygenase 1 (HO-1), via the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was observed in the PIC-treated group. Our results suggest that PIC is a potential CRC-blocking agent due to its ability to alleviate DNA damage, decrease intracellular ROS production, modulate the metabolism and detoxification of B[a]P, and activate the Nrf2 signaling pathway in B[a]P-induced NCM460 cells.
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Benzo(a)pireno , Estilbenos , Humanos , Benzo(a)pireno/toxicidad , Benzo(a)pireno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Daño del ADN , Estilbenos/farmacología , Estilbenos/metabolismo , Células Epiteliales/metabolismo , Antioxidantes/metabolismo , Glutatión/metabolismoRESUMEN
Soil dissolved organic carbon (DOC) is the most active part in forest soil carbon pool, the responses of which to climate warming has profound effects on forest carbon cycling. Based on a manipulative soil warming experiment in subtropical evergreen broad-leaved forests, we collected soil solutions in situ and used ultraviolet-visible, infrared and three-dimensional fluorescence spectroscopy analyses to explore the effects of soil warming (+4 â, 1 year) on soil DOC quantity and quality along the soil profile. The results showed that soil DOC flux remained constant along the soil profile. Soil DOC mainly included two humic-like fractions and one microbial metabolite. Warming significantly decreased soil DOC flux and the abundance of aromatic and hydrophobic components, and increased the amount of low molecular weight carbohydrates. Furthermore, soil warming increased the relative proportion of humic-like fractions in the surface soil layer (0-10 cm) and microbial metabolite in the deep soil layer (30-40 cm), indicating that warming might accelerate microbial turnover in the deep layer. Overall, soil warming not only decreased soil DOC content, but also simplified the composition of soil DOC in subtropical evergreen broad-leaved forests.
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Materia Orgánica Disuelta , Suelo , Suelo/química , Nitrógeno/análisis , Bosques , Carbono/análisis , ChinaRESUMEN
Inflammatory bowel disease has become a significant health concern across the globe, causing frequent and long-term harm to the digestive system. This study evaluated the effect of piceatannol (PIC) and 3'-hydroxypterostilbene (HPSB) on dextran sulfate sodium (DSS)-induced colitis in mice and investigated whether their effects are exerted through the amelioration of gut barrier dysfunction to reduce the severity of colitis. The findings showed that both PIC and HPSB attenuated inflammation by inhibiting the TNF-α/NF-κB/MLC pathway and reducing NLRP3 inflammasome activation. However, PIC was comparably effective in modulating tight junctions. The results may be attributed to the effect of PIC on reducing cell apoptosis-associated protein expression, including Bax/Bcl-2 and caspase-3 activation. Furthermore, microbiota analysis revealed that both PIC and HPSB increased representative probiotic species, including Akkermansiaceae and Lactobacillus intestinalis, and exhibited inhibitory effects on several bacterial species (Spiroplasmataceae and Acholeplasmataceae). Based on linear discriminant analysis effect size, butyrate-producing bacteria were identified as a biomarker in the PIC group. Overall, the results demonstrated that PIC repressed inflammation, inhibited cell apoptosis, and regulated microbiota composition. Consequently, PIC is more effective in maintaining gut barrier integrity than HPSB, and it is a promising ingredient in the development of functional food for colitis prevention.
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Colitis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Animales , Ratones , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colon/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Inflamación , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Ratones Endogámicos C57BLRESUMEN
Different treatments of harvest residues will change the quantity and quality of soil organic matter, with direct or indirect effects on the composition and content of soil nutrient. Nitrogen is one of the most important soil nutrients. However, the response of soil organic nitrogen fractions to different harvest residue treatments is still unclear. In this study, harvest residue treatments, including harvest residue removed, residue retained and residue burnt, were set up after clear-cutting a 50-year-old mature Cunninghamia lanceolata forest in Sanming City, Fujian, China. The H2SO4 hydrolysis method was used to determine soil organic nitrogen fractions and their driving factors in the 0-10 cm and 10-20 cm soil layers after 5 years of harvest residue treatments. The results showed that residue retained treatment significantly enhanced the contents of soil organic nitrogen and its liable fractions. In the 0-10 cm soil layer, soil organic nitrogen content under residue retained treatment (3.36 g·kg-1) was 1.5 and 1.3 times as those of residue removed and residue burnt treatments, respectively. Residue retained treatment had the highest contents of labile nitrogen â and â ¡ fractions. In 10-20 cm soil layer, the contents of soil organic nitrogen and labile nitrogen â ¡ fraction were also significantly higher in residue retained treatment (2.20, 0.73 g·kg-1) than that in residue removed and residue burnt treatments. The labile nitrogen index â ¡ in residue retained treatment (33.9%) was significantly higher than in residue burnt treatment (26.1%). The contents of total carbon, dissolved organic carbon, dissolved organic nitrogen, microbial biomass under residue retained treatment were the highest in both soil layers. Compared with residue removed treatment, residue retained treatment significantly enhanced the abundance of soil bacteria (Gram-positive bacteria and Gram-negative bacteria) in 0-10 cm soil layer. In 10-20 cm soil layer, residue retained treatment had the highest content of fungi and the lowest content of actinomycetes. Pearson analysis showed that there were significant positive correlations of labile fractions of soil organic nitrogen with total carbon, dissolved organic carbon, dissolved organic nitrogen, microbial biomass carbon, microbial biomass nitrogen, bacteria (Gram-positive bacteria, Gram-negative bacteria), and fungi, and negative correlations with actinomycetes. It was concluded that the retention of harvest residue was beneficial to increase the content of soil organic nitrogen and labile fractions, improve soil biochemical properties and had a positive effect on soil microbial community composition. Retention of harvest residue was an effective management measure to maintain soil fertility and improve forest productivity.
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Actinobacteria , Cunninghamia , Carbono/análisis , China , Bosques , Nitrógeno/análisis , Suelo/química , Microbiología del SueloRESUMEN
Obesity is characterized by metabolic disorder and accompanying an altered and less diverse gut microbiota composition during a fat-enriched diet. Recent studies indicated that sulphated polysaccharide prevents high-fat diet (HFD) induced obesity, reduces metabolic disorder, and restores the gut microbiota. However, there are few studies about Ulva prolifera polysaccharide (UPP) may induce anti-obesogenic effects. Therefore, the present study investigates the enzymatic extracted UPP effects in HFD-fed mice. The results showed that UPP considerably slowed down the HFD-induced weight gain and improved metabolic disorders in HFD-fed mice. Notably, the effects were associated with lower body weight gain, reduced adipose tissue hypertrophy, triglyceride concentration in liver and systemic low-grade inflammation, and improved fasting blood glucose. Moreover, our result reveals that UPP may elevate the expression of AMPK via adiponectin activation. Interestingly, we found that UPP may induce PPARα agonist to enhance ß-oxidation since the elevation of CPT-1 and PPARα expression simultaneously. Meanwhile, gut microbiota analysis revealed UPP promoted the growth of Parasutterella, Feacalibaculum, and Bifidobacterium, and reduced the abundance of Acetatifactor, Tyzerella, Ruminococcus_1, and Desulfovibrio. The changes in microbiota may have a positively correlated effect on improving obesity and metabolic abnormalities. UPP may prevent HFD-induced obesity and associated metabolic diseases, as well as modulate the composition of gut microbiota to facilitate the growth of probiotics.
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Microbioma Gastrointestinal , Ulva , Adiponectina/metabolismo , Adiponectina/farmacología , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , PPAR alfa/metabolismo , Polisacáridos/farmacología , Regulación hacia ArribaRESUMEN
Prescribing a ketogenic diet (KD) is a century-old dietary intervention mainly used in the context of intractable epilepsy. The classic KD and its variants regained popularity in recent decades, and they are considered potentially beneficial in a variety of neurological conditions other than epilepsy. Many patients with multiple sclerosis (MS) have attempted diet modification for better control of their disease, although evidence thus far remains insufficient to recommend a specific diet for these patients. The results of 3 pilot clinical trials of KD therapy for MS, as well as several related studies, have been reported in recent years. The preliminary findings suggest that KD is safe, feasible, and potentially neuroprotective and disease-modifying for patients with MS. Research on corresponding rodent models has also lent support to the efficacy of KD in the prevention and treatment of experimental autoimmune encephalomyelitis and toxin-induced inflammatory demyelinating conditions in the brain. Furthermore, the animal studies have yielded mechanistic insights into the molecular mechanisms of KD action in relevant situations, paving the way for precision nutrition. Herein we review and synthesize recent advances and also identify unresolved issues, such as the roles of adipokines and gut microbiota, in this field. Hopefully this panoramic view of current understanding can inform future research directions and clinical practice with regard to KD in MS and related conditions.
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Dieta Cetogénica , Epilepsia , Microbioma Gastrointestinal , Esclerosis Múltiple , Adipoquinas , Animales , Dieta Cetogénica/métodos , HumanosAsunto(s)
Citratos , Ácido Cítrico , Citratos/metabolismo , Ácido Cítrico/metabolismo , Hígado/metabolismoRESUMEN
SCOPE: This study aims to investigate whether S-allylcysteine (SAC) exerts chemoprophylactic effects on foodborne carcinogenicity caused by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in normal human colonic mucosal epithelial cells. METHODS AND RESULTS: Cellular thermal shift assays show that SAC has an affinity for the Kelch-like ECH-associated protein 1 (Keap1) protein. Moreover, SAC may also dampen the binding of Keap1 and NF-E2-related factor 2 (Nrf2) by inhibiting p-p38 and increasing the phosphorylation of extracellular signal regulated kinases 1/2 (ERK1/2) and protein kinase B (AKT), thereby inducing Nrf2/heme oxygenase-1 (HO-1) signaling and upregulating the ratio of glutathione (GSH) to GSH/GSSG (oxidized glutathione), which inhibits PhIP-induced oxidative stress and DNA damage. In addition, SAC significantly downregulates the aryl hydrocarbon receptor signaling pathway, suggesting that SAC may potentially impede the metabolic transformation of carcinogens. CONCLUSION: Collectively, these findings suggest that SAC protects against PhIP-induced reactive oxygen species production and DNA damage by modulating the Nrf2/AhR signaling pathway, which may have significant potential as a novel chemopreventive agent.