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Berberine (BBR) is a traditional Chinese herb with broad antimicrobial activity. Gut microbiota plays an important role in the metabolism of bile acids and cholesterol. Our study investigated the effects of BBR on alleviating cholesterol and bile acid metabolism disorders induced by high cholesterol diet in mice. Adult male C57BL/6J mice fed with high cholesterol diet (HC) containing 1.25 % cholesterol (HC group) or fed with chow diet containing 0.02 % cholesterol (Chow group) served as controls. BBR50 and BBR100 group mice were fed with HC, and oral BBR daily at doses of 50 or 100 mg/kg respectively for 8 weeks. The results showed that BBR could reshape the homeostasis and composition of gut microbiota. The abundance of Clostridium genera was significantly inhibited by BBR, which resulted in a significant reduction of secondary bile acids within the enterohepatic circulation and a significant lower hydrophobic index of bile acids. The absorption of cholesterol in intestine, the deposition of cholesterol in liver and the excretion of cholesterol in biliary tract were significantly inhibited by BBR, which promoted the unsaturation of cholesterol in bile. These findings suggest the potential utility of BBR as a functional food to alleviate the negative effects of high cholesterol diet.
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Berberina , Ácidos y Sales Biliares , Colesterol en la Dieta , Colesterol , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Animales , Berberina/farmacología , Ácidos y Sales Biliares/metabolismo , Masculino , Colesterol/metabolismo , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Colesterol en la Dieta/efectos adversos , Colesterol en la Dieta/metabolismo , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/efectos de los fármacosRESUMEN
BACKGROUND: Cholesterol gallstone disease is a common disease. Reducing cholesterol burden is important to prevent/treat gallstone. In this study, we investigated the application of diosgenin (DG) to prevent the formation of gallstone in mice. METHODS: Adult male C57BL/6J mice were fed with the lithogenic diet (LD) only or LD supplemented with DG or ezetimibe for 8 weeks. Incidences of gallstone formation were documented. Intestine and liver tissues were collected to measure the lipid contents and expression of genes in cholesterol metabolism. Caco2 cells were treated with DG to monitor the regulation on cholesterol absorption and the transcriptional regulation of Npc1l1 gene. Changes of gut microbiota by DG was analyzed. Intraperitoneal injection of LPS on mice was performed to verify its effects on STAT3 activation and Npc1l1 expression in the small intestine. RESULTS: LD led to 100% formation of gallstones in mice. In comparison, dietary DG or ezetimibe supplementary completely prevents gallstones formation. DG inhibited intestinal cholesterol absorption in mice as well as in Caco2 cells by down-regulation of Npc1l1 expression. DG could directly inhibit phosphorylation of STAT3 and its transcriptional regulation of Npc1l1 expression. Furthermore, DG could modulate gut microbiota profiles and LPS mediated STAT3 activation and Npc1l1 expression. CONCLUSION: Our results demonstrated that dietary DG could inhibit intestinal cholesterol absorption through decreasing NPC1L1 expression to prevent cholesterol gallstone formation.
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Diosgenina , Cálculos Biliares , Humanos , Ratones , Masculino , Animales , Cálculos Biliares/prevención & control , Cálculos Biliares/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Diosgenina/farmacología , Diosgenina/metabolismo , Células CACO-2 , Lipopolisacáridos , Ratones Endogámicos C57BL , Intestinos , Colesterol , Dieta , Ezetimiba/farmacología , Ezetimiba/metabolismo , Hígado/metabolismoRESUMEN
Soybean (Glycine max) is an important oil crop, but the regulatory mechanisms underlying seed oil accumulation remain unclear. We identified a member of the GmWRI1s transcription factor family, GmWRI1c, that is involved in regulating soybean oil content and nodulation. Overexpression of GmWRI1c in soybean hairy roots increased the expression of genes involved in glycolysis and de novo lipogenesis, the proportion of palmitic acid (16:0), and the number of root nodules. The effect of GmWRI1c in increasing the number of root nodules via regulating the proportion of palmitic acid was confirmed in a recombinant inbred line (RIL) population. GmWRI1c shows abundant sequence diversity and has likely undergone artificial selection during domestication. An association analysis revealed a correlation between seed oil content and five linked natural variations (Hap1/Hap2) in the GmWRI1c promoter region. Natural variations in the GmWRI1c promoter were strongly associated with the GmWRI1c transcript level, with higher GmWRI1c transcript levels in lines carrying GmWRI1cHap1 than in those carrying GmWRI1cHap2. The effects of GmWRI1c alleles on seed oil content were confirmed in natural and RIL populations. We identified a favourable GmWRI1c allele that can be used to breed new varieties with increased seed oil content and nodulation.
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Glycine max , Ácido Palmítico , Glycine max/metabolismo , Ácido Palmítico/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fitomejoramiento , Aceite de Soja/metabolismoRESUMEN
INTRODUCTION AND OBJECTIVES: Gallbladder disease is a common disease with high prevalence. Majority of gallbladder disease is due to gallstone. Though genetics are believed to play a role in its pathogenesis, the contribution of environmental pressures in early life to the development of this disease in adulthood has not been ever investigated. This study aimed to clarify the risk of maternal smoking exposure in association with gallbladder disease in adulthood. The interaction of maternal smoking and own smoking during adulthood on this association was studied as well. PATIENTS AND METHODS: A total of 286,731 eligible participants from the UK Biobank population-based cohort were included. Multivariable Cox regression analysis were used to examine the HR and 95% CI with adjustment for covariates. RESULT: During a median of 8.8 years follow-up, 7110 incident cases of gallbladder disease including 6800 (95.6%) gallstone were identified. Maternal smoking was associated with increased risk of incident total gallbladder disease (HR = 1.13; 95%CI: 1.06 - 1.21; P = 0.0002) as well as gallstones (HR = 1.13; 95%CI: 1.06 -1.21; P = 0.0003) in adulthood. Compared with those who were neither exposed to maternal smoking nor own smoking, subjects adherence to no smoking during adulthood but having maternal smoking exposure still had increased risk of total gallbladder disease (HR = 1.21; 95%CI: 1.1-1.34, P=0.0001) and gallstones (HR = 1.21; 95%CI: 1.1-1.35, P=0.0001). CONCLUSION: The present study using large prospective cohort data from UK Biobank, for the first time, demonstrated maternal smoking exposure bringing elevated risk of incident total gallbladder disease/gallstone in adulthood.
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Bancos de Muestras Biológicas/estadística & datos numéricos , Enfermedades de la Vesícula Biliar/etiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Medición de Riesgo/métodos , Fumar/efectos adversos , Femenino , Estudios de Seguimiento , Enfermedades de la Vesícula Biliar/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Embarazo , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Reino Unido/epidemiologíaRESUMEN
X-ray repair cross-complementing group 1 (Xrcc1), a key DNA repair gene, plays a vital role in maintaining genomic stability and is highly expressed in the early stages of spermatogenesis, but the exact functions remain elusive. Here we generated primordial germ cell-specific Xrcc1 knockout (cXrcc1-/-) mice to elucidate the effects of Xrcc1 on spermatogenesis. We demonstrated that Xrcc1 deficiency results in infertility in male mice due to impaired spermatogenesis. We found that cXrcc1-/- mice exhibited smaller size of testes as well as lower sperm concentration and motility than the wild-type mice. Mechanistically, we demonstrated that Xrcc1 deficiency in primordial germ cells induced elevated levels of reactive oxygen species, mitochondria dysfunction, apoptosis, and loss of stemness of spermatogonial stem cells (SSCs) in testes. In Xrcc1-deficienct SSCs, elevated oxidative stress and mitochondrial dysfunction could be partially reversed by treatment with the antioxidant N-acetylcysteine (NAC), whereas NAC treatment did not restore the fertility or ameliorate the apoptosis caused by loss of Xrcc1. Overall, our findings provided new insights into understanding the crucial role of Xrcc1 during spermatogenesis.-Xu, C., Xu, J., Ji, G., Liu, Q., Shao, W., Chen, Y., Gu, J., Weng, Z., Zhang, X., Wang, Y., Gu, A. Deficiency of X-ray repair cross-complementing group 1 in primordial germ cells contributes to male infertility.
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Células Germinativas/metabolismo , Infertilidad Masculina/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genética , Acetilcisteína/farmacología , Animales , Apoptosis , Femenino , Células Germinativas/efectos de los fármacos , Masculino , Ratones , Ratones Noqueados , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Testículo/citología , Testículo/metabolismoRESUMEN
Cholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially Desulfovibrionales) in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying Desulfovibrionales is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of Desulfovibrionales, H2S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying Desulfovibrionales present induction of hepatic expression of cholesterol transporters Abcg5/g8 to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota, Desulfovibrionales, as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism.
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Ácidos y Sales Biliares/metabolismo , Colesterol/biosíntesis , Digestión/fisiología , Cálculos Biliares/metabolismo , Microbioma Gastrointestinal/fisiología , Animales , Bilis/metabolismo , Colelitiasis , Colesterol 7-alfa-Hidroxilasa/genética , Colesterol 7-alfa-Hidroxilasa/metabolismo , Desulfovibrionales/fisiología , Heces/microbiología , Absorción Intestinal , Metabolismo de los Lípidos , Lipogénesis , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , MicrobiotaRESUMEN
Increasing evidence suggests that cholecystectomy is an independent risk factor for non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms that lead to hepatic lipid deposition after cholecystectomy are unclear. In this study, adult male C57BL/6J mice that underwent a cholecystectomy or sham operation were fed either a high-fat diet (HFD) or a chow diet for 56 days. Significantly increased steatohepatitis, liver/body weight ratio, hepatic triglycerides, and glucose intolerance were observed in postcholecystectomy mice fed the HFD. Notable alterations in the composition of gut microbiota after cholecystectomy were observed in both HFD- and chow-diet-fed mice. Our results indicate that cholecystectomy alters the gut microbiota profile, which might contribute to the development of NAFLD in mice.
RESUMEN
Cholesterol gallstone disease is a common global condition. This study investigated the role of plant sterols (PS) in the prevention of gallstone formation and the underlying mechanisms. Adult male mice were fed a lithogenic diet (LD) alone or supplemented with PS (LD-ps), phospholipids (LD-pl) or both PS and phospholipids (LD-ps/pl) for 8 weeks. Incidences of gallstone formation were compared among the groups. Lipids in the bile, liver and serum were analyzed. The expression of genes involved in cholesterol absorption, transport and metabolism in the liver and small intestine was determined. The incidences of gallstone formation were 100% (10/10), 20% (2/10), 100% (10/10) and 40% (4/10) in the LD, LD-ps, LD-pl and LD-ps/pl groups, respectively. Serum cholesterol and intestinal cholesterol absorption were decreased in PS-supplemented mice. The expression of genes related to cholesterol transport and metabolism in the liver was down-regulated by dietary PS. PS supplementation decreased Niemann-Pick C1-like 1 expression in the small intestine and reduced intestinal cholesterol absorption. Our results demonstrated that PS could inhibit intestinal cholesterol absorption and thus prevent cholesterol gallstone formation.
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Colesterol/metabolismo , Cálculos Biliares/prevención & control , Absorción Intestinal/efectos de los fármacos , Fitosteroles/farmacología , Animales , Colesterol/administración & dosificación , Colesterol/efectos adversos , Dieta , Suplementos Dietéticos , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Gallstone disease is a worldwide common disease. However, the knowledge concerning the gallbladder in the pathogenesis of cholesterol gallstone formation remains limited. In this study, using single-cell RNA sequencing (scRNA-seq) to obtain the transcriptome of gallbladder cells, we showed cellular heterogeneity and transcriptomic dynamics in murine gallbladder cells during the process of lithogenesis. Our results indicated gallbladder walls were subjected to remodeling during the process of lithogenesis. The major molecular events that happened included proliferation of epithelial cells, infiltration of immune-cells, activation of angiogenesis, and extracellular matrix modulation. Furthermore, we observed partial reversal of gallbladder cell transcriptomes by ursodeoxycholic acid treatment. This work thus provides novel and integral knowledges on the cellular changes during lithogenesis, which is of great significance to the understanding of pathogenesis and treatment of cholesterol gallstone.
RESUMEN
Background: Hepatic lipid metabolism regulates biliary composition and influences the formation of cholesterol gallstones. The genes Hmgcr and Cyp7a1, which encode key liver enzymes, are regulated by circadian rhythm-related transcription factors. We aimed to investigate the effect of circadian rhythm disruption on hepatic cholesterol and bile acid metabolism and the incidence of cholesterol stone formation. Methods: Adult male C57BL/6J mice were fed either a lithogenic diet (LD) only during the sleep phase (time-restricted lithogenic diet feeding, TRF) or an LD ad libitum (non-time-restricted lithogenic diet feeding, nTRF) for 4 weeks. Food consumption, body mass gain, and the incidence of gallstones were assessed. Circulating metabolic parameters, lipid accumulation in the liver, the circadian expression of hepatic clock and metabolic genes, and the gut microbiota were analyzed. Results: TRF caused a dysregulation of the circadian rhythm in the mice, characterized by significant differences in the circadian expression patterns of clock-related genes. In TRF mice, the circadian rhythms in the expression of genes involved in bile acid and cholesterol metabolism were disrupted, as was the circadian rhythm of the gut microbiota. These changes were associated with high biliary cholesterol content, which promoted gallstone formation in the TRF mice. Conclusion: Disordered circadian rhythm is associated with abnormal hepatic bile acid and cholesterol metabolism in mice, which promotes gallstone formation.
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Trastornos Cronobiológicos/complicaciones , Cálculos Biliares/etiología , Microbioma Gastrointestinal , Metabolismo de los Lípidos , Hígado/metabolismo , Animales , Colesterol/metabolismo , Trastornos Cronobiológicos/etiología , Trastornos Cronobiológicos/metabolismo , Trastornos Cronobiológicos/microbiología , Ritmo Circadiano/fisiología , Dieta/efectos adversos , Cálculos Biliares/metabolismo , Cálculos Biliares/microbiología , Microbioma Gastrointestinal/fisiología , Metabolismo de los Lípidos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Factores de TiempoRESUMEN
Perfluorooctanoic acid (PFOA) is an emerging organic pollutant (EOP) hazardous to human health. Effects of maternal PFOA exposure on offspring as well as the underlying mechanisms remain unclear. In this study, ICR mouse models of gestational low PFOA exposure (0.05 mg/kg/day) were established to investigate the roles on metabolic disorders of offspring. Body weight, body composition, hepatic lipid levels, transcriptome and metabolome were analyzed. Expression of genes related to lipid metabolism, inflammasome formation and gut barrier integrity were measured. Furthermore, oral administration of chlorogenic acid (CGA) (100 mg/kg/day) was performed to observe the rescue effect on lipid disorders caused by PFOA exposure. Our findings demonstrated that gestational exposure to PFOA resulted in obesity, hepatic inflammation, disorders of lipid metabolism, and disruption of gut barrier integrity in male offspring. Notably, these adverse effects were attenuated by CGA supplementation. These data suggested that PFOA exposure during early life stage induced potential risks for later onset of obesity and metabolic disorder which could be ameliorated by CGA treatment.
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Ácido Clorogénico , Fluorocarburos , Animales , Caprilatos/toxicidad , Femenino , Fluorocarburos/toxicidad , Humanos , Hígado , Masculino , Ratones , Ratones Endogámicos ICR , Obesidad/inducido químicamenteRESUMEN
Bisphenol A (BPA) has a variety of adverse effects on human health; therefore, BPA analogs are increasingly used as replacements. Notably, recent studies have revealed that BPA exposure induced hepatic lipid accumulation, but few studies are available regarding the similar effects of other bisphenol analogues (BPs). Thus, in the present study, a high-content screening (HCS) assay was performed to simultaneously evaluate the hepatic lipid accumulation of 13 BPs in vitro. The BPs induced lipid deposition in HepG2 cells ranking as below: 4,4'-thiodiphenol (TDP) < bisphenol S (BPS) < 4,4'-dihydroxybenzophenone (DHBP) < tetrabromobisphenol A (TBBPA) < tetrachlorobisphenol A (TCBPA) < bisphenol E (BPE) < bisphenol F (BPF) < bisphenol B (BPB) < bisphenol AF (BPAF) < bisphenol A (BPA) < bisphenol C (BPC) < tetramethylbisphenol A (TMBPA) < bisphenol AP (BPAP). Meanwhile, Oil Red O staining and triacylglycerol detection further validated the lipid accumulation elicited by the latter 8 BPs, which exhibited the more significant effects on lipid deposition. Mechanistically, significantly increased expressions of genes involved in fatty acid synthesis and nuclear receptors and decreased levels of genes associated with fatty acid ß-oxidation were observed under BPs treatment. Therefore, the present work is the first to systematically provide direct evidence for BPs-induced hepatic lipid accumulation in vitro via HCS, which can be helpful for safety assessments of BPs.
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Compuestos de Bencidrilo/toxicidad , Ensayos Analíticos de Alto Rendimiento , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Fenoles/toxicidad , Supervivencia Celular/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Células Hep G2 , HumanosRESUMEN
Trimethylamine-N-oxide (TMAO) is a metabolite derived from trimethylamine (TMA), which is first produced by gut microbiota and then oxidized by flavin-containing monooxygenase 3 (FMO3) in the liver. TMAO may contribute to the development of diseases such as atherosclerosis because of its role in regulating lipid metabolism. In this study, we found that high plasma TMAO levels were positively associated with the presence of gallstone disease in humans. We further found increased hepatic FMO3 expression and elevated plasma TMAO level in a gallstone-susceptible strain of mice C57BL/6J fed a lithogenic diet (LD), but not in a gallstone-resistant strain of mice AKR/J. Dietary supplementation of TMAO or its precursor choline increased hepatic FMO3 expression and plasma TMAO levels and induced hepatic canalicular cholesterol transporters ATP binding cassette (Abc) g5 and g8 expression in mice. Up-regulation of ABCG5 and ABCG8 expression was observed in hepatocytes incubated with TMAO in vitro. Additionally, in AKR/J mice fed a LD supplemented with 0.3% TMAO, the incidence of gallstones rose up to 70% compared with 0% in AKR/J mice fed only a LD. This was associated with increased hepatic Abcg5 and g8 expression induced by TMAO. Our study demonstrated TMAO could be associated with increased hepatic Abcg5/g8 expression, biliary cholesterol hypersecretion and gallstone formation.
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Cálculos Biliares/metabolismo , Metilaminas/metabolismo , Oxigenasas/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/metabolismo , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Aterosclerosis/metabolismo , Colesterol/metabolismo , Dieta , Modelos Animales de Enfermedad , Femenino , Cálculos Biliares/patología , Microbioma Gastrointestinal/fisiología , Regulación de la Expresión Génica , Humanos , Lipoproteínas/metabolismo , Hígado/metabolismo , Masculino , Metilaminas/sangre , Ratones Endogámicos AKR , Ratones Endogámicos C57BL , Oxigenasas/genética , ARN Mensajero/metabolismoRESUMEN
2,4-Dichlorophenoxyacetic acid is one of the most widely used herbicides. Its impact on health is increasingly attracting great attentions. This study aimed to investigate the effect of 2,4-dichlorophenoxyacetic acid on glucose metabolism in HepG2 cells and the underlying mechanism. After 24 h exposure to 2,4-dichlorophenoxyacetic acid, glycogen was measured by PAS staining and glucose by ELISA in HepG2 cells. The expression of genes involved in glucose metabolism was measured by real-time PCR, Western blotting, and immunofluorescence. HepG2 cells presented more extracellular glucose consumption and glycogen content after exposed to 2,4-dichlorophenoxyacetic acid. Expression of gluconeogenesis-related genes, FoxO1, and CREB is significantly elevated. Moreover, PPARß was up-regulated dose-dependently. SiRNA knockdown of PPARß completely rescued the increase of glycogen accumulation and glucose uptake, and the up-regulation of FOXO1 and CREB expression. Our findings propose novel mechanisms that 2,4-dichlorophenoxyacetic acid causes glucose metabolism dysfunction through PPARß in HepG2 cells.
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Ácido 2,4-Diclorofenoxiacético , Glucosa/metabolismo , Glucógeno/metabolismo , Células Hep G2/metabolismo , Herbicidas/química , PPAR-beta/química , Animales , Gluconeogénesis , Glucosa/química , Glucógeno/química , Células Hep G2/química , Herbicidas/metabolismo , Humanos , PPAR-beta/metabolismo , Regulación hacia ArribaRESUMEN
Excessive cholesterol contributes to the development of cardiovascular diseases. Berberine (BBR) has been reported to regulate cholesterol homeostasis. Here, we found that BBR could ameliorate the hepatic autophagic flux blockade caused by cholesterol overloading. The underlying mechanism included lowering hepatic cholesterol level, modulating the cholesterol distribution targeting the plasma membrane by decreasing sterol carrier protein 2 expression and inhibiting cyclooxygenase 2-mediated production of prostaglandin metabolites, which decreased the phosphorylation of Akt/mTOR. Our study provides evidences that BBR could be a therapeutic agent for protecting liver under cholesterol overloading via the regulation of autophagic flux.
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Autofagia/efectos de los fármacos , Berberina/farmacología , Ciclooxigenasa 2/metabolismo , Hígado/metabolismo , Prostaglandinas/metabolismo , Animales , Colesterol/metabolismo , Colesterol/farmacología , Ciclooxigenasa 2/química , Dieta Alta en Grasa , Células Hep G2 , Humanos , Hígado/efectos de los fármacos , Masculino , Ratones , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína Sequestosoma-1/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Global prevalence of obesity has been increasing dramatically in all ages. Although traditional causes for obesity development have been studied widely, it is unclear whether environmental exposure of substances such as trace heavy metals affects obesity development among children and adolescents so far. Data from the National Health and Nutrition Examination Survey (1999-2011) were retrieved, and 6602 US children were analyzed in this study. Urinary level of nine trace heavy metals, including barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, and tungsten, was analyzed for their association with the prevalence of obesity among children aged 6-19 years. Multiple logistic regression was performed to assess the associations adjusted for age, race/ethnicity, gender, urinary creatinine, PIR, serum cotinine, and television, video game, and computer usage. A remarkable association was found between barium exposure (OR 1.43; 95% CI 1.09-1.88; P < 0.001) and obesity in children aged 6-19 years. Negative association was observed between cadmium (OR 0.46; 95% CI 0.33-0.64; P < 0.001), cobalt (OR 0.56; 95% CI: 0.41-0.76; P < 0.001), and lead (OR 0.57; 95% CI 0.41-0.78; P = 0.018), and obesity. All the negative associations were stronger in the 6-12 years group than in the 13-19 years group. The present study demonstrated that barium might increase the occurrence of obesity, but cadmium, cobalt, and lead caused weight loss among children. The results imply that trace heavy metals may represent critical risk factors for the development of obesity, especially in the area that the state of metal contamination is serious.
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Metales Pesados/orina , Obesidad/epidemiología , Adolescente , Bario/orina , Cadmio/orina , Niño , Cobalto/orina , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Plomo/orina , Masculino , Encuestas Nutricionales , Factores de Riesgo , Estados Unidos , Adulto JovenRESUMEN
p,p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and ß-hexachlorocyclohexane (ß-HCH) were two predominant organochlorine pesticides (OCPs) metabolites in human body associated with disorders of fatty acid metabolism. However, the underlying mechanisms have not been fully clarified. In this study, adult male C57BL/6 mice were exposed to low dose of p, p'-DDE and ß-HCH for 8 wk. OCPs accumulation in organs, hepatic fatty acid composition, tricarboxylic acid cycle (TCA) metabolites and other metabolite profiles were analyzed. Expression levels of genes involved in hepatic lipogenesis and ß-oxidation were measured. Mitochondrial function was evaluated in HepG2 cells exposed to OCPs. High accumulation of p, p'-DDE and ß-HCH was found in liver and damaged mitochondria was observed under electron microscopy. Expression of genes in fatty acid synthesis increased and that in mitochondrial fatty acid ß-oxidation decreased in OCPs treatment groups. OCPs changed metabolite profiles in liver tissues, varied hepatic fatty acid compositions and levels of several TCA cycle metabolites. Furthermore, MitoTracker Green fluorescence, ATP levels, mitochondrial membrane potential and OCR decreased in HepG2 cells exposed to OCPs. In conclusion, chronic exposure to OCPs at doses equivalent to internal exposures in humans impaired mitochondrial function, decreased fatty acid ß-oxidation and aggravated disorders of fatty acid metabolism.
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Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hidrocarburos Clorados/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Plaguicidas/farmacología , Animales , Ciclo del Ácido Cítrico/efectos de los fármacos , Progresión de la Enfermedad , Ácidos Grasos/metabolismo , Hepatocitos/patología , Hexaclorociclohexano/metabolismo , Hexaclorociclohexano/farmacología , Humanos , Trastornos del Metabolismo de los Lípidos/etiología , Trastornos del Metabolismo de los Lípidos/metabolismo , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Ratones , Oxidación-ReducciónRESUMEN
Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and ß-hexachlorocyclohexane (ß-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p'-DDE and ß-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human.
Asunto(s)
Ácidos y Sales Biliares/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Hidrocarburos Clorados/toxicidad , Plaguicidas/toxicidad , Animales , Diclorodifenil Dicloroetileno/análisis , Hexaclorociclohexano/metabolismo , Hexaclorociclohexano/toxicidad , Hidrocarburos Clorados/análisis , Hidrocarburos Clorados/metabolismo , Intestinos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/química , Masculino , Ratones , Ratones Endogámicos C57BL , Plaguicidas/análisis , Plaguicidas/metabolismo , ARN Ribosómico 16SRESUMEN
The International Agency for Research on Cancer and the World Health Organization have designated airborne particulates, including particulates of median aerodynamic diameter ≤ 2.5 µm (PM2.5), as Group 1 carcinogens. It has not been determined, however, whether exposure to ambient PM2.5 is associated with an increase in respiratory related diseases. This meta-analysis assessed the association between exposure to ambient fine particulate matter (PM2.5) and the risk of respiratory tract diseases, using relevant articles extracted from PubMed, Web of Science, and Embase. In results, of the 1,126 articles originally identified, 35 (3.1%) were included in this meta-analysis. PM2.5 was found to be associated with respiratory tract diseases. After subdivision by age group, respiratory tract disease, and continent, PM2.5 was strongly associated with respiratory tract diseases in children, in persons with cough, lower respiratory illness, and wheezing, and in individuals from North America, Europe, and Asia. The risk of respiratory tract diseases was greater for exposure to traffic-related than non-traffic-related air pollution. In children, the pooled relative risk (RR) represented significant increases in wheezing (8.2%), cough (7.5%), and lower respiratory illness (15.3%). The pooled RRs in children were 1.091 (95%CI: 1.049, 1.135) for exposure to <25 µg/m3 PM2.5, and 1.126 (95%CI: 1.067, 1.190) for exposure to ≥ 25 µg/m3 PM2.5. In conclusion, exposure to ambient PM2.5 was significantly associated with the development of respiratory tract diseases, especially in children exposed to high concentrations of PM2.5.
RESUMEN
Multi-walled carbon nanotubes (MWCNTs) have been widely used in many fields and were reported to cause reversible testis damage in mice at high-dose. However the reproductive effects of low dose MWCNTs remained elusive. Herein, we used the mice spermatocyte cell line (GC-2spd) to assess the reproductive effects of MWCNTs. Size distribution, zeta potential, and intensity of MWCNTs were characterized. A maximal concentration of 0.5 µg/mL MWCNTs was found to be nonlethal to GC-2spd. At this dose, cell cycles and the ROS levels were in normal status. We also found MWCNTs accumulated in mitochondria, which caused potential mitochondrial DNA damage in spermatocyte. Furthermore, the expression level of mitochondria-related genes, the oxygen consumption rate, and cellular ATP content were declined compared to controls, even at the nonlethal dose. Our results suggested for the first time that, in germ cells, mitochondrion was a cellular organelle that accumulated MWCNTs.