Assuntos
Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Vemurafenib/uso terapêutico , Suspensão de Tratamento , Idoso , Progressão da Doença , Esquema de Medicação , Evolução Fatal , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/cirurgia , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Medição de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodosRESUMO
We investigated whether replicative senescence of endothelial cells contributed to the pathogenesis of atherosclerosis in human umbilical vein endothelial cells (HUVECs). HUVECs at a population-doubling level of 30 (PDL30) divided much more slowly than those at PDL9. The percentage of SA-ß-Gal-positive cells and the mRNA expression levels of PAI-1 and p21 at PDL30 were significantly higher than those at PDL9. The changes induced by aging were evaluated according to the mRNA expression level of genes related to the endothelial cell function. The expression level of many adhesion molecules promoting monocytic adhesion was significantly increased, and monocytic adhesion on HUVECs was found to be significantly promoted by aging. Monocytic adhesion is an essential early event in the development of atherosclerosis, and our results suggest that replicative senescence of the vascular endothelial cells induced increased expression of adhesion molecules. The consequent increase in monocytic adhesion may then promote the pathogenesis of atherosclerosis.
Assuntos
Aterosclerose/metabolismo , Moléculas de Adesão Celular/metabolismo , Senescência Celular/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Aterosclerose/genética , Adesão Celular , Moléculas de Adesão Celular/genética , Divisão Celular , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/genética , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Expressão Gênica , Humanos , Monócitos/citologia , Monócitos/fisiologia , Inibidor 1 de Ativador de Plasminogênio/genética , Veias Umbilicais/citologia , Veias Umbilicais/metabolismoRESUMO
Lipid metabolism in a child may be altered when the mother has a high-fat diet (HFD), but it is unclear whether the lipid metabolism of future offspring (grandchildren) is also changed under these circumstances. In this study, we examined the influence of intake of an HFD beyond one generation on offspring in normal mice. Parent mice fed an HFD were bred and the resultant second and third generations were also fed an HFD. The diets used in the study had approximately 20% more energy than a standard chow diet. Changes in lipid metabolism were examined in each generation. Intake of an HFD from generation to generation promoted lipid accumulation in the white adipose tissue of female mice, increased lipid, glucose and insulin levels in the serum, increased the activities of enzymes associated with fatty acid metabolism in the liver, promoted lipid accumulation in hepatocytes and adipocytes and increased the mRNA levels of Cdkn1a in the liver and white adipose tissue. These results suggest that activation of Cdkn1a promoted lipid accumulation in the liver and white adipose tissue of third-generation female mice that were offspring from earlier generations fed HFDs. Moreover, intake of a high-energy diet beyond one generation led to offspring with obesity, fatty liver and hyperinsulinemia.
Assuntos
Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Animais , Glicemia , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/fisiopatologia , Feminino , Hiperinsulinismo/etiologia , Hiperinsulinismo/fisiopatologia , Insulina/sangue , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Obesidade/etiologia , Obesidade/fisiopatologiaRESUMO
Various factors have been reported to influence lipid metabolism and cause metabolic syndrome. However, the influence of allergy on the liver that plays important role of lipid metabolism has not been clarified. The aim of this study was to examine the influence of allergy on lipid metabolism of liver. A model of atopic dermatitis was developed in the NC/Nga mouse using picryl chloride to induce allergy. Lipid metabolism parameters were measured and the mechanism of changes in these parameters was examined using DNA microarray analysis and quantitative reverse transcriptase PCR. Triacylglycerol accumulation was promoted in the liver in the mouse atopic dermatitis model despite reductions in food intake, body weight gain, and serum glucose. As this mechanism, it was thought that atopic dermatitis caused the suppression of fatty acid ß-oxidation. These results suggest that atopic dermatitis causes lipid accumulation in the liver.