RESUMEN
AIMS: Epidemiology shows that gender affects the incidence of food allergy. However, there is a lack of evidence of gender differences in food allergies and little is known about the mechanisms. The aim of this study was to excavate potential reasons for gender differences in food allergy based on estrogen. MAIN METHODS: Female and male BALB/c mice sensitized with ovalbumin (OVA) were established to analyze the difference in food allergy. The systemic anaphylactic, including OVA-specific IgE, OVA-specific IgG, histamine, and cytokines, was assessed using an enzyme-linked immunosorbent assay (ELISA). ELISA also detected the estradiol in serum. Western blotting and immunofluorescence were used to detect the estrogen receptor. Peroxisome proliferator-activated receptor gamma (PPARγ) implicated in immune homeostasis and nuclear factor kappa-B (NF-κB) were determined by western blotting. Immunohistochemistry and hematoxylin-eosin (H&E) staining were used to detect zonula occludens-1 (ZO-1), tryptase, forkhead box protein P3 (Foxp3), and intestinal morphology, respectively. KEY FINDINGS: Female mice were more vulnerable to food allergy. Female mice treated with OVA did exhibit more serious systemic anaphylaxis than male mice. We observed increased levels of estradiol in serum, estrogen receptor, NF-κB, and decreased levels of PPAR γ in female mice. Furthermore, the intestinal mucosal integrity and intestinal permeability were more impaired in female mice treated with OVA than male mice. SIGNIFICANCE: Clarify the mechanism of gender differences in food allergies can provide targets in female mice and provide personalized diagnosis, management, and treatment of food allergy for female mice.
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Hipersensibilidad a los Alimentos/patología , Inflamación/patología , Intestinos/patología , FN-kappa B/análisis , PPAR gamma/análisis , Animales , Femenino , Hipersensibilidad a los Alimentos/etiología , Inflamación/etiología , Masculino , Ratones , Ratones Endogámicos BALB C , Caracteres Sexuales , Factores SexualesRESUMEN
Docosahexaenoic acid (DHA, 22:6) and eicosapentaenoic acid (EPA, 20:5) have been reported to improve metabolic disorders, but their differential effects on anti-obesity under insulin resistance (IR) are still unclear. We fed IR mice with high-fat diet with added 1%, 2%, 4% (w/w) DHA or EPA for 12 weeks. Changes in weight, food intake, white adipose tissue (WAT), liver and blood lipids were assessed. GPR120 and PPARγ of WAT were evaluated to explore the related molecular mechanisms of DHA and EPA for anti-obesity in IR mice. 1%DHA and 1%EPA inhibit adipogenesis by down-regulating GPR120; 4%DHA stimulates browning of WAT and improves IR and inflammatory infiltration by up-regulating PPARγ; 4%EPA exerts its anti-obesity effect by mechanisms independent of PPARγ and GPR120 signaling.
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Fármacos Antiobesidad/administración & dosificación , Dieta Alta en Grasa , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Resistencia a la Insulina , Obesidad/tratamiento farmacológico , Adipogénesis/efectos de los fármacos , Adipoquinas/genética , Tejido Adiposo Blanco/química , Tejido Adiposo Blanco/efectos de los fármacos , Animales , Hígado Graso/tratamiento farmacológico , Expresión Génica/efectos de los fármacos , Inflamación/genética , Metabolismo de los Lípidos/genética , Lípidos/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/fisiopatología , PPAR gamma/análisis , PPAR gamma/efectos de los fármacos , Receptores Acoplados a Proteínas G/análisis , Receptores Acoplados a Proteínas G/efectos de los fármacosAsunto(s)
Alopecia/metabolismo , Cicatriz/metabolismo , PPAR gamma/biosíntesis , Glándulas Sebáceas , Adolescente , Adulto , Anciano , Alopecia/complicaciones , Alopecia/patología , Niño , Cicatriz/complicaciones , Cicatriz/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , PPAR gamma/análisis , Estudios RetrospectivosRESUMEN
Nelumbinis Semen (NS, the seeds of Nelumbo nucifera) extract is a traditional Korean medicine with anti-oxidant activity. The present study examined the anti-obesity and antidiabetic effects of NS powder in high-fat diet (HFD)-induced obese C57BL/6 mice. Mice (n = 8/group) were fed a normal diet (CON), HFD, HFD containing 5% NS powder (HFD-NS5%), or HFD containing 10% NS powder (HFD-NS10%) for 12 weeks. Food intake was relatively higher in groups HFD-NS5% and HFD-NS10%, while the food efficiency ratio was highest in group HFD (p < 0.05). HFD-NS5% reduced the body weight (-39.1%) and fat weight (-26.6%), including epididymal fat and perirenal fat, and lowered the serum triglyceride levels (-20.6%) compared with HFD. Groups HFD-NS5% and HFD-NS10% showed hepatoprotective properties, reducing the serum ALT levels (p < 0.05) and fat globules (size and number) in the liver compared with group HFD. HFD-NS5% and HFD-NS10% regulated the blood glucose, improved the glucose intolerance, and showed a 12.5% and 15.0% reduction in the area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT), and a 26.8% and 47.3% improvement in homeostatic model assessment insulin resistance (HOMA-IR), respectively, compared with HFD (p < 0.05). Regarding the expressions of genes related to anti-obesity and antidiabetes, there was a 1.7- and 1.3-fold increase in PPAR-α protein expression, 1.4- and 1.6-fold increase in PPAR-γ protein expression, and 0.7- and 0.6-fold decrease in TNF-α protein expression, respectively, following HFD-NS5% and HFD-NS10% treatments, compared with HFD, and GLUT4 protein expression increased relative to CON (p < 0.05). These results comprehensively provide the fundamental data for NS powder's functional and health-promoting benefits associated with anti-obesity and antidiabetes.
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Fármacos Antiobesidad/administración & dosificación , Medicamentos Herbarios Chinos/química , Hipoglucemiantes/administración & dosificación , Obesidad/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Animales , Glucemia/análisis , Dieta Alta en Grasa , Transportador de Glucosa de Tipo 4/análisis , Resistencia a la Insulina , Lípidos/sangre , Hígado/química , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/patología , PPAR alfa/análisis , PPAR gamma/análisis , República de Corea , Factor de Necrosis Tumoral alfa/análisis , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: The present study was designed to investigate the effects of Berberis vulgaris (BV) juice consumption on plasma levels of insulin-like growth factor (IGF-1), IGF-binding proteins (IGFBPs), and the expression of PPAR-γ, VEGF and HIF in women with benign breast disease. METHODS: This parallel design randomized, double-blind controlled clinical trial was conducted on 85 eligible patients diagnosed with benign breast disease. They were assigned randomly into either BV juice group (n = 44, BV juice: 480 ml/day) or placebo group (n = 41, BV placebo juice: 480 ml/day) for 8 weeks intervention. Participants, caregivers and those who assessed laboratory analyses were blinded to the assignments. Plasma levels of biomarkers were measured at baseline and after 8 weeks by ELISA. Quantitative real-time PCR was used to measure the fold change in the expression of each interested gene. RESULTS: The compliance of participants was 95.2% and 40 available subjects analyzed in each group at last. Relative treatment (RT) effects for BV juice caused 16% fall in IGF-1 concentration and 37% reduction in the ratio of IGF-1/1GFBP1. Absolute treatment effect expressed 111 ng/ml increased mean differences of IGFBP-3 between BV group and placebo. Plasma level of PPAR-γ increased in both groups but it was not significant. Fold changes in the expressions of PPAR-γ, VEGF and HIF showed down-regulation in the intervention group compared to placebos (P < 0.05). CONCLUSIONS: The BV juice intervention over 8 weeks was accompanied by acceptable efficacy and decreased plasma IGF-1, and IGF-1/IGFBP-1 ratio partly could be assigned to enhanced IGFBP-1 level in women with BBD. The intervention caused reductions in the expression levels of PPAR, VEGF, and HIF which are remarkable genomic changes to potentially prevent breast tumorigenesis. TRIAL REGISTRATION: IRCT2012110511335N2. Registered 10 July 2013 (retrospectively registered).
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Berberis , Neoplasias de la Mama , Jugos de Frutas y Vegetales , Adulto , Mama/química , Mama/patología , Neoplasias de la Mama/química , Neoplasias de la Mama/dietoterapia , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Factor 1 Inducible por Hipoxia/análisis , Factor 1 Inducible por Hipoxia/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/metabolismo , Persona de Mediana Edad , PPAR gamma/análisis , PPAR gamma/metabolismo , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto JovenRESUMEN
Background and Objectives: The use of the dopamine-partial agonist subclass (also termed dopamine stabilizers) of atypical antipsychotics for the treatment of negative schizophrenia symptoms and some mood disorders has increased recently. Similar to other second-generation antipsychotics (SGAs), aripiprazole (ARI) and cariprazine (CAR) also influence food intake, but the peripheral effects of these drugs on adipose-tissue homeostasis, including adipokine secretion as well as lipo- and adipogenesis, are not fully elucidated. In this study, we explored the adipocyte-related mechanisms induced by second-generation antipsychotics (SGAs), leading to changes in peripheral signals involved in energy homeostasis. Materials and Methods: CAR, a new SGA, was compared with ARI and olanzapine (OLA), using cell cultures to study adipogenesis, and the expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ) was measured in adipocytes derived from mouse fibroblasts, by western blotting on days 7, 14, and 21 postinduction. The triglyceride (TG) content of the cells was also evaluated on day 15 using Oil Red O staining, and the adiponectin (AN) content in the cell culture supernatants was quantified on days 7 and 15 by enzyme-linked immunosorbent assay. Cells were treated with two concentrations of ARI (0.5 and 20 µg/mL), OLA (1 and 20 µg/mL), and CAR (0.1 and 2 µg/mL). Results: Both concentrations of ARI and OLA, as well as the lower concentration of CAR, significantly increased the TG contents. The AN levels in the supernatants were significantly increased by the higher concentration of ARI on days 7 and 15 (p < 0.05). Although PPAR-γ levels were not significantly affected by ARI and OLA, the lower concentration of CAR induced a significant time-dependent decrease in PPAR-γ expression (p < 0.05). Conclusions: The in vitro adipogenesis considered from TG accumulation, AN secretion, and PPAR-γ expression was differently influenced by ARI, CAR, and OLA. Understanding the adipocyte-related mechanisms of antipsychotics could contribute to understanding their weight-influencing effect.
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Aripiprazol/uso terapéutico , Fibroblastos/efectos de los fármacos , Olanzapina/uso terapéutico , Piperazinas/uso terapéutico , Adiponectina/análisis , Adiponectina/sangre , Animales , Aripiprazol/administración & dosificación , Aripiprazol/farmacología , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Fibroblastos/patología , Ratones , Trastornos del Humor/tratamiento farmacológico , Olanzapina/administración & dosificación , Olanzapina/farmacología , PPAR gamma/análisis , PPAR gamma/sangre , Piperazinas/administración & dosificación , Piperazinas/farmacología , Triglicéridos/análisis , Triglicéridos/sangreRESUMEN
Clinical and animal studies have suggested efficacies of common bean (Phaseolus vulgaris) consumption on weight loss. Fermentation of common bean-derived dietary fiber by gut microbiota is proposed to mitigate obesity; however, the mechanism of action is unclear. The objective of this study was to investigate whether and how fecal fermentation of common bean-derived dietary fiber impacts adipogenesis in a cell model. Dietary fiber was generated by in vitro digestion of cooked, lyophilized common bean flour, followed by anaerobic fermentation with the use of fresh feces from healthy mice without antibiotics treatment. The murine 3T3-L1 cells were induced to differentiate in the presence of the fermentation products. Treatment of the fecal fermentation products inhibited adipocyte differentiation and lipid accumulation in a dose- and time-dependent manner. The fermentation products decreased (P<.05) protein levels of two key transcription factors for adipogenesis, CCAAT/enhancer binding protein α and peroxisome proliferator-activated receptor γ by 79-92% and 78-90%, respectively, and one of their downstream targets fatty acid binding protein 4 by 49-86% and 63-98% at protein and mRNA levels, respectively, during the time course. In contrast, the fermentation products increased (P<.05) levels of two proteins promoting energy expenditure, peroxisome proliferator-activated receptor δ (71-91%) on days 2 and 4 and mitochondrial uncoupling protein 2 (1.1-1.2 fold) on days 4-8. Altogether, fecal fermentation of dietary fiber derived from in vitro digestion of common bean temporally and dose-dependently inhibits adipogenesis and key adipogenic transactivators, but activates two energy expenditure proteins in 3T3-L1 cells.
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Adipogénesis/efectos de los fármacos , Fibras de la Dieta/metabolismo , Metabolismo Energético/efectos de los fármacos , Heces/microbiología , Fermentación , Phaseolus/química , Células 3T3-L1 , Adipocitos/fisiología , Animales , Proteína alfa Potenciadora de Unión a CCAAT/análisis , Proteína alfa Potenciadora de Unión a CCAAT/genética , Diferenciación Celular/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Ratones , PPAR delta/análisis , PPAR delta/genética , PPAR gamma/análisis , PPAR gamma/genética , ARN Mensajero/análisis , Proteína Desacopladora 2/análisis , Proteína Desacopladora 2/genéticaRESUMEN
To explore PPAR-γ and SOX-2 transcription factors expression in placenta according to maternal anti-Toxoplasma gondii serological profile during pregnancy and pregnancy outcome. The study included 240 placentas, grouped according to IgM and IgG serostatus and then subgrouped according to pregnancy outcome that varied between miscarriages, premature labour, stillbirth and giving birth to CNS anomaly or apparently healthy neonates. Samples were H&E stained and histopathologically scored blindly. PPAR-γ expression was measured by ELISA, while SOX-2-positive nuclei were stained immunohistochemically to be calculated by ImageJ. The mean pathological score was significantly higher in IgM+ve and IgG rising than IgG-ve and persistent low groups. Former groups showed significantly higher PPAR-γ (mean = 258.63, 227.11). However, PPAR-γ was higher in apparently healthy neonate subgroups. SOX-2 was significantly lower in IgM+ve and IgG rising groups (mean = 12.87, 43.13) and associated with obvious fibrosis. SOX-2 lowest count was in CNS anomaly subgroup. PPAR-γ and SOX-2 changes may give clues of how Toxoplasma induces pathogenesis during vertical transmission. Triggering PPAR-γ expression may be a tool to downregulate the inflammatory response and establish a metabolically permissive cellular environment for Toxoplasma persistence. Low SOX-2 is suspected to disturb placental mesenchymal stem cells pluripotency and neuroectoderm development.
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Anticuerpos Antiprotozoarios/sangre , PPAR gamma/análisis , Placenta/metabolismo , Complicaciones Parasitarias del Embarazo/parasitología , Factores de Transcripción SOXB1/análisis , Toxoplasmosis/patología , Toxoplasmosis/transmisión , Adolescente , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Células Madre Mesenquimatosas/citología , Embarazo , Resultado del Embarazo , Toxoplasma/inmunología , Adulto JovenRESUMEN
The present study aimed to investigate the possible effects and underlying molecular mechanism of BushenYizhi formula (BSYZ), a traditional Chinese medicine, on agerelated degeneration of brain physiology in senescenceaccelerated mouse prone 8 (SAMP8) mice. SAMP8 mice (age, 6 months) were administered BSYZ (1.46, 2.92 and 5.84 g/kg/day) for 30 days. Morris water maze and stepdown tests demonstrated that BSYZ significantly improved memory impairments in SAMP8 mice. In addition, BSYZ significantly enhanced the expression levels of peroxisome proliferatoractivated receptorγ and Bcell lymphoma extralarge, and downregulated the expression levels of inflammatory mediators, glial fibrillary acidic protein, cyclooxygenase2, nuclear factorκB and interleukin1ß in the brain compared with untreated SAMP8 mice. Furthermore, BSYZ reversed disordered superoxide dismutase activity, malondialdehyde content and glutathione peroxidase activity, and ameliorated apoptosis and histological alterations. The present study indicated that BSYZ may attenuate cognitive impairment in SAMP8 mice, and modulate inflammation, oxidative stress and neuronal apoptosis. These results suggested that BSYZ may have the potential to be further developed into a therapeutic agent for protection against agerelated neurodegenerative diseases.
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Envejecimiento Prematuro/complicaciones , Envejecimiento Prematuro/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Inflamación/tratamiento farmacológico , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Química Encefálica/efectos de los fármacos , Ciclooxigenasa 2/análisis , Proteína Ácida Fibrilar de la Glía/análisis , Inflamación/etiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , PPAR gamma/análisisAsunto(s)
Carcinoma Hepatocelular , Ácidos Nucleicos Libres de Células , Hepatitis B Crónica , Cirrosis Hepática , Hígado , Enfermedad del Hígado Graso no Alcohólico , PPAR gamma , Biomarcadores/análisis , Biomarcadores/metabolismo , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/etnología , Ácidos Nucleicos Libres de Células/análisis , Ácidos Nucleicos Libres de Células/metabolismo , Metilación de ADN , Progresión de la Enfermedad , Femenino , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/etnología , Humanos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/etnología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/etnología , PPAR gamma/análisis , PPAR gamma/metabolismo , Regiones Promotoras Genéticas , Turquía/epidemiologíaRESUMEN
BACKGROUND: Immune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear. MAIN AIM: To identify potential differential intra-/intercellular biochemical pathways controlling immune-inflammatory response and their oxidative-nitrosative impact on SCH patients, compared with bipolar disorder (BD) patients and healthy controls (HC). METHODS: Cross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)]. STATISTICAL ANALYSIS: ANCOVA (or Quade test) controlling for age and gender when comparing the three groups, and controlling for age, gender, length of illness, cigarettes per day, and body mass index (BMI) when comparing SCH and BD. RESULTS: Pro-inflammatory biomarkers: Expression of COX-1 was statistically higher in SCH and BD than HC (P<0.0001; P<0.0001); NFκB and PGE2 were statistically higher in SCH compared with BD (P=0.001; P<0.0001) and HC (P=0.003; P<0.0001); NLRP3 was higher in BD than HC (P=0.005); and CPR showed a gradient among the three groups. Anti-inflammatory biomarkers: BD patients had lower PPARγ and higher 15d-PGJ2 levels than SCH (P=0.005; P=0.008) and HC (P=0.001; P=0.001). Differences between SCH and BD: previous markers of SCH (NFκB and PGE2) and BD (PPARγ and 15d-PGJ2) remained statistically significant and, interestingly, iNOS and COX-2 (pro-inflammatory biomarkers) levels were statistically higher in SCH than BD (P=0.019; P=0.040). CONCLUSIONS: This study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.
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Trastorno Bipolar/inmunología , Trastorno Bipolar/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Esquizofrenia/inmunología , Esquizofrenia/metabolismo , Adulto , Biomarcadores/análisis , Trastorno Bipolar/patología , Trastorno Bipolar/psicología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Inflamación/patología , Inflamación/psicología , Masculino , Persona de Mediana Edad , PPAR gamma/análisis , Prostaglandina D2/análogos & derivados , Prostaglandina D2/análisis , Esquizofrenia/patología , Psicología del Esquizofrénico , Adulto JovenRESUMEN
The present study investigated whether the protective effect of umbelliferone could regulate myocardial injury following ischemiareperfusion and improve mitochondrial respiratory function, thereby relieving myocardial injury following ischemiareperfusion in rats. In the present study, the extent of inflammation and oxidative stress were analyzed using ELISA. Western blot analysis was employed to investigate the protein expression levels of the PYD domainscontaining protein 3 (NLRP3) inflammasome and peroxisome proliferatoractivated receptor-γ (PPARγ). Compared with the myocardial injury following ischemiareperfusion group, umbelliferone significantly prevented myocardial injury, inhibited oxidative stress markers (superoxide dismutase and malondialdehyde), reduced inflammation (tumor necrosis factorα and interleukin6) and myocardial apoptosis levels (caspase3/9 and apoptosis regular Bcell lymphoma2associated X protein) in the myocardial injury following ischemiareperfusion group of rats. Umbelliferone treatment also suppressed NACHT, LRR and NLRP3 inflammasome activation and induced PPARγ expression. The results of the present study suggested that the protective effect of umbelliferone may ameliorate myocardial injury following ischemiareperfusion in the rat through the suppression of the NLRP3 inflammasome and upregulating PPARγ expression.
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Antiinflamatorios/uso terapéutico , Cardiotónicos/uso terapéutico , Inflamasomas/antagonistas & inhibidores , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , PPAR gamma/inmunología , Umbeliferonas/uso terapéutico , Animales , Antioxidantes/uso terapéutico , Apoptosis/efectos de los fármacos , Inflamasomas/inmunología , Masculino , Daño por Reperfusión Miocárdica/inmunología , Daño por Reperfusión Miocárdica/patología , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , PPAR gamma/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
Naringin, a flavonoid, is the effective pharmaceutical ingredient of drynaria, with the effects of healing fractures, strengthening bones and promoting kidney function. The aim of the present study was to investigate the potential effect of naringin on steroidinduced avascular necrosis of the femoral head (SANFH). Treatment with naringin markedly protected against the steroidinduced decrease in serum osteocalcin levels, and the rate of osteonecrosis in a model of SANFH. In addition, naringin decreased the total cholesterol and low density lipoprotein/high density lipoprotein ratio in the SANFH rabbit. It was observed that naringin markedly inhibited caspase3 activity, increased runtrelated transcription factor 2 and transcription factor sp7 mRNA expression, promoted alkaline phosphatase activity and upregulated collagen I, peroxisome proliferatoractivated receptor (PPAR) γ2, neurogenic locus notch homolog protein (Notch), ßcatenin and phosphorylatedRacα serine/threonine protein kinase protein expression in the SANFH rabbit. The results of the present study demonstrated that naringin protects against SANFH through upregulation of PPARγ2 and activation of the Notch signaling pathway, and may be a useful addition to the treatment options for diseases of the femoral head.
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Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/tratamiento farmacológico , Flavanonas/uso terapéutico , PPAR gamma/metabolismo , Sustancias Protectoras/uso terapéutico , Receptores Notch/metabolismo , Transducción de Señal/efectos de los fármacos , Esteroides/efectos adversos , Animales , Cabeza Femoral/efectos de los fármacos , Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/etiología , Necrosis de la Cabeza Femoral/metabolismo , Masculino , PPAR gamma/análisis , Conejos , Receptores Notch/análisis , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND & AIMS: In addition to environmental and psychosocial factors, it is known that genetic factors can also influence the regulation of energy metabolism, body composition and determination of excess weight. The objective of this study was to evaluate the influence of UCP3, PLIN1 and PPARG2 genes on the substrates oxidation in women with grade III obesity after hypocaloric dietary intervention. SUBJECTS/METHODS: This is a longitudinal study with 21 women, divided into two groups: Intervention Group (G1): 11 obese women (Body Mass Index (BMI) ≥40 kg/m2), and Control Group (G2): 10 eutrophic women (BMI between 18.5 kg/m2 and 24.9 kg/m2). Weight (kg), height (m), BMI (kg/m2), substrate oxidation (by Indirect Calorimetry) and abdominal subcutaneous adipose tissue were collected before and after the intervention. For the dietary intervention, the patients were hospitalized for 6 weeks receiving 1200 kcal/day. RESULTS: There was a significant weight loss (8.4 ± 4.3 kg - 5.2 ± 1.8%) and reduction of UCP3 expression after hypocaloric dietary intervention. There was a positive correlation between carbohydrate oxidation and UCP3 (r = 0.609; p = 0.04), PLIN1 (r = 0.882; p = 0.00) and PPARG2 (r = 0.791; p = 0.00) expression before dietary intervention and with UCP3 (r = 0.682; p = 0.02) and PLIN1 (r = 0.745; p = 0.00) genes after 6 weeks of intervention. There was a negative correlation between lipid oxidation and PLIN1 (r = -0.755; p = 0.00) and PPARG2 (r = 0.664; p = 0.02) expression before dietary intervention and negative correlation with PLIN1 (r = 0.730; p = 0.02) expression after 6 weeks of hypocaloric diet. CONCLUSION: Hypocaloric diet reduces UCP3 expression in individuals with obesity and the UCP3, PLIN1 and PPARG2 expression correlate positively with carbohydrate oxidation and negatively with lipid oxidation.
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Dieta Reductora , Obesidad , PPAR gamma/metabolismo , Perilipina-1/metabolismo , Proteína Desacopladora 3/metabolismo , Adulto , Calorimetría Indirecta , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Obesidad/dietoterapia , Obesidad/metabolismo , Obesidad/fisiopatología , Oxidación-Reducción , Consumo de Oxígeno/fisiología , PPAR gamma/análisis , PPAR gamma/genética , Perilipina-1/análisis , Perilipina-1/genética , Proteína Desacopladora 3/análisis , Proteína Desacopladora 3/genética , Pérdida de Peso/fisiología , Adulto JovenRESUMEN
Citral is a small molecule present in various citrus species, with reported anti-hyperlipidemic and anti-inflammation effects. Here, the effect of intraperitoneal (IP) administration of citral is evaluated in a mouse model of non-alcoholic steatosis. Male NMRI mice were divided into the following groups (n = 12): normal control group (NC) receiving a normal diet; high-fat emulsion group (HF) receiving high fat diet for four weeks; positive control group (C+) receiving HF diet for four weeks and then shifted to normal diet with IP-administered silymarin (80 mg/kg) for four weeks; sham group receiving HF diet for four weeks and then shifted to normal diet for four weeks; and EC1, EC2, and EC3 groups receiving HF diet for four weeks and then shifted to normal diet with IP-administered citral doses of 5, 10, and 20 mg/kg, respectively. HF diet resulted in steatohepatitis with impaired lipid profile, high glucose levels and insulin resistance, impaired liver enzymes, antioxidants, adiponectin and leptin levels, decreased PPARα level, and fibrosis in the liver tissue. Upon treatment with citral, improvement in condition was observed in a dose-dependent manner-both at histological level and in the serum of treated animals. and the PPARα level was also increased.
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Animales , Masculino , Ratas , Expresión Génica/fisiología , PPAR gamma/análisis , Enfermedad Hepática en Estado Terminal/diagnóstico , Silimarina/farmacología , Citrus , Enfermedad del Hígado Graso no Alcohólico/diagnósticoRESUMEN
Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is associated with endothelial dysfunction. The prevalence of OSA is linked to an epidemic of obesity. CIH has recently been reported to cause endothelial dysfunction in diet-induced obese animals by exaggerating oxidative stress and inflammation, but the underlying mechanism remains unclear. PPAR-γ, a ligand-inducible transcription factor that exerts anti-oxidant and anti-inflammatory effects, is down-regulated in the peripheral tissues in diet-induce obesity. We tested the hypothesis that down-regulation of vascular PPAR-γ in diet-induced obesity enhances inflammation and oxidative stress in response to CIH, resulting in endothelial dysfunction. Male C57BL/6 mice were fed either a high-fat diet (HFD) or a low-fat diet (LFD) and simultaneously exposed to CIH or intermittent air for 6 weeks. An additional HFD group received a combination of CIH and PPAR-γ agonist pioglitazone for 6 weeks. Endothelial-dependent vasodilation was impaired only in HFD group exposed to CIH, compared with other groups, but was restored by concomitant pioglitazone treatment. Molecular studies revealed that vascular PPAR-γ expression and activity were reduced in HFD groups, compared with LFD groups, but were reversed by pioglitazone treatment. In addition, CIH elevated vascular expression of NADPH oxidase 4 and dihydroethidium fluorescence, and increased expression of proinflammatory cytokines TNF-α and IL-1ß in both LFD and HFD groups, but these increases was significantly greater in HFD group, along with decreased vascular eNOS activity. Pioglitazone treatment of HFD group prevented CIH-induced changes in above molecular markers. The results suggest that HFD-induced obesity down-regulates vascular PPAR-γ, which results in exaggerated oxidative stress and inflammation in response to CIH, contributing to endothelial dysfunction. This finding may provide new insights into the mechanisms by which OSA induces endothelial dysfunction and other cardiovascular disease in patients with obesity.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Endotelio Vascular/fisiopatología , Hipoxia/complicaciones , Obesidad/etiología , Obesidad/fisiopatología , PPAR gamma/metabolismo , Animales , Regulación hacia Abajo , Endotelio Vascular/metabolismo , Hipoxia/metabolismo , Hipoxia/fisiopatología , Inflamación/complicaciones , Inflamación/metabolismo , Inflamación/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Obesidad/metabolismo , Estrés Oxidativo , PPAR gamma/análisis , Apnea Obstructiva del SueñoRESUMEN
BACKGROUND/AIMS: This study was designed to investigate the therapeutic effect of traditional Chinese medication Qiliqiangxin (QLQX) on adverse cardiac remodeling after myocardial infarction (MI) in bilateral ovariectomized (OVX) female mice. METHODS: Eight-week old female C57BL/6 mice were operated to ligate the left anterior descending coronary artery seven days after bilateral ovariectomy and were orally administered either QLQX or vehicle. 21 days after ligation, echocardiography was performed to evaluate the heart function of all mice. Masson's Trichrome staining was applied to evaluate myocardial fibrosis. Collagen deposition was determined by the mRNA level of Collagen I, Collagen III and α-SMA using real-time quantitative polymerase chain reaction (qPCR). Myocardial apoptosis was examined by the protein level of Bax, Bcl2 and the Bcl2/Bax ratio using western blotting. RESULTS: These mice displayed a significant reduction in heart function, increased myocardial fibrosis and apoptosis, and decreased expression of peroxisome proliferator activated receptor γ (PPARγ) in the heart tissue, which could be reversed by QLQX treatment. Inhibition of PPAR reduced QLQX-mediated cardio-protective effects, while PPARγ activation did not further enhance the beneficial effect of QLQX. Furthermore, QLQX upregulated 9 genes (Cd36, Fatp, Pdk4, Acadm, Acadl, Acadvl, Cpt1a, Cpt1b and Cpt2) facilitating energy metabolism in the MI hearts of the OVX mice and 5 (Acadm, Acadl, Cpt1a, Cpt1b, Cpt2) of the 9 genes were the downstream targets of PPARγ. CONCLUSION: The present study indicates that QLQX has a treatment effect on pathological remodeling post MI in bilateral OVX female mice via activation of PPARγ, suggesting that QLQX may be a promising prescription for the treatment of postmenopausal women suffering from MI.
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Medicamentos Herbarios Chinos/uso terapéutico , Corazón/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , PPAR gamma/metabolismo , Animales , Femenino , Ratones , Ratones Endogámicos C57BL , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/metabolismo , Miocardio/patología , Ovariectomía , PPAR gamma/análisis , Remodelación Ventricular/efectos de los fármacosRESUMEN
Long-term peritoneal dialysis (PD) leads to ultrafiltration failure (UFF). Peritoneal mesothelial cells, which form the innermost monolayer of the peritoneal cavity, have been shown to regulate various responses, including inflammation, in UFF. The present study was designed to investigate the effect of the peroxisome proliferatoractivated receptorγ (PPARγ) agonist, rosiglitazone, on peritoneal dialysis solution (PDS)induced injuries in rat peritoneal mesothelial cells (RPMCs). RPMCs were cultured for different durations and with different concentrations of PDS. The gene expression levels of aquaporin1 (AQP1) and zonula occluden1 (ZO1) were determined using reverse transcriptionquantitative polymerase chain reaction analysis. The protein levels of AQP1, ZO1 and PPARγ were measured using western blot analysis. Interleukin (IL)6 and IL8 were detected using ELISA. The RPMCs were damaged by stimulation with 4.25% PDS for 72 h. The expression levels of AQP1 and ZO1 were increased, and the secretion of IL6 and IL8 were decreased by rosiglitazone. The use of the PPARγ inhibitor, GW9662, completely prevented the effects of rosiglitazone. These results indicated that PDS exposure stimulated an inflammatory response in the RPMCs. The PPARγ activator, rosiglitazone, appeared to relieve the injury by inhibiting inflammation, and regulating the expression of AQP1 and ZO1, however further investigations are required to elucidate the potential underlying mechanism.
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Soluciones para Diálisis/efectos adversos , Células Epiteliales/efectos de los fármacos , PPAR gamma/agonistas , Diálisis Peritoneal/efectos adversos , Peritoneo/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Tiazolidinedionas/uso terapéutico , Animales , Acuaporina 1/análisis , Acuaporina 1/genética , Células Epiteliales/patología , Interleucina-6/análisis , Interleucina-6/metabolismo , Interleucina-8/análisis , Interleucina-8/metabolismo , Masculino , PPAR gamma/análisis , PPAR gamma/metabolismo , Peritoneo/citología , Peritoneo/patología , ARN Mensajero/genética , Ratas Sprague-Dawley , Rosiglitazona , Proteína de la Zonula Occludens-1/análisis , Proteína de la Zonula Occludens-1/genéticaRESUMEN
BACKGROUND: From ancient times, marine algae have emerged as alternative medicine and foods, contains the rich source of natural products like proteins, vitamins, and secondary metabolites, especially Chlorella vulgaris (C. vulgaris) contains numerous anti-inflammatory, antioxidants and wound healing substances. Type 2 diabetes mellitus is closely associated with adipogenesis and their factors. Hence, we aimed to investigate the chemical constituents and adipogenic modulatory properties of C. vulgaris in 3T3-L1 pre-adipocytes. RESULTS: We analysed chemical constituents in ethanolic extract of C. vulgaris (EECV) by LC-MS. Results revealed that the EECV contains few triterpenoids and saponin compounds. Further, the effect of EECV on lipid accumulation along with genes and proteins expressions which are associated with adipogenesis and lipogenesis were evaluated using oil red O staining, qPCR and western blot techniques. The data indicated that that EECV treatment increased differentiation and lipid accumulation in 3T3-L1 cells, which indicates positive regulation of adipogenic and lipogenic activity. These increases were associated with up-regulation of PPAR-γ2, C/EBP-α, adiponectin, FAS, and leptin mRNA and protein expressions. Also, EECV treatments increased the concentration of glycerol releases as compared with control cells. Troglitazone is a PPAR-γ agonist that stimulates the PPAR-γ2, adiponectin, and GLUT-4 expressions. Similarly, EECV treatments significantly upregulated PPAR-γ2, adiponectin, GLUT-4 expressions and glucose utilization. Further, EECV treatment decreased AMPK-α expression as compared with control and metformin treated cells. CONCLUSION: The present research findings confirmed that the EECV effectively modulates the lipid accumulation and differentiation in 3T3-L1 cells through AMPK-α mediated signalling pathway.
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Células 3T3-L1/efectos de los fármacos , Chlorella vulgaris/química , Extractos Vegetales/farmacología , Algas Marinas/química , Células 3T3-L1/fisiología , Proteínas Quinasas Activadas por AMP/análisis , Proteínas Quinasas Activadas por AMP/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adiponectina/análisis , Adiponectina/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Diabetes Mellitus Tipo 2/metabolismo , Regulación hacia Abajo , Expresión Génica , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4/análisis , Transportador de Glucosa de Tipo 4/efectos de los fármacos , Transportador de Glucosa de Tipo 4/metabolismo , Ratones , PPAR gamma/análisis , PPAR gamma/efectos de los fármacos , PPAR gamma/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Regulación hacia ArribaRESUMEN
Escherichia coli K1 meningitis continues to be a major threat to neonatal health. Previous studies demonstrated that outer membrane protein A (OmpA) of E. coli K1 interacts with endothelial cell glycoprotein 96 (Ecgp96) in the blood-brain barrier to enter the central nervous system. Here we show that the interaction between OmpA and Ecgp96 downregulates peroxisome proliferator-activated receptor γ (PPAR-γ) and glucose transporter 1 (GLUT-1) levels in human brain microvascular endothelial cells, causing disruption of barrier integrity and inhibition of glucose uptake. The suppression of PPAR-γ and GLUT-1 by the bacteria in the brain microvessels of newborn mice causes extensive pathophysiology owing to interleukin 6 production. Pretreatment with partial or selective PPAR-γ agonists ameliorate the pathological outcomes of infection by suppressing interleukin 6 production in the brain. Thus, inhibition of PPAR-γ and GLUT-1 by E. coli K1 is a novel pathogenic mechanism in meningitis, and pharmacological upregulation of PPAR-γ and GLUT-1 levels may provide novel therapeutic avenues.