Assuntos
Hipertensão Portal/patologia , Pólipos Intestinais/patologia , Doenças do Jejuno/patologia , Anemia/complicações , Anemia/etiologia , Endoscopia por Cápsula , Enteroscopia de Duplo Balão , Humanos , Hipertensão Portal/complicações , Pólipos Intestinais/complicações , Pólipos Intestinais/diagnóstico , Doenças do Jejuno/complicações , Doenças do Jejuno/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: It is common for alcoholic patients to have excess iron accumulation in the liver, which may contribute to the development of alcoholic liver disease (ALD). However, the mechanism of hepatic iron uptake in ALD is still obscure. Recently, a novel iron-regulatory hormone hepcidin was found that suppresses the absorption of iron from the small intestine and the release of iron from macrophages. To elucidate the contribution of hepcidin toward the hepatic excess iron accumulation in ALD, we examined whether alcohol loading affects hepcidin expression both in ALD patients and in an ethanol-fed mouse model. METHODS: Serum prohepcidin concentration was quantified by enzyme-linked immunosorbent assay. Hepatic hepcidin-1 and hepcidin-2 mRNA expressions in mouse liver were evaluated by quantitative real-time reverse-transcriptase polymerase chain reaction method. The protein expression of prohepcidin in mouse liver was examined immunohistochemically by rabbit antimouse prohepcidin antibody. RESULTS: Serum prohepcidin concentration in ALD was significantly lower than that in healthy subjects (p<0.001). Especially, serum prohepcidin concentrations were decreased in the patients whose serum ferritin value was high. In the ethanol-fed mouse model, hepatic hepcidin-1 mRNA expression was significantly lower than that in control (p=0.04). Prohepcidin was expressed in the cytoplasm of hepatocytes of mice liver tissue sections, and its expression was decreased after ethanol loading. CONCLUSION: Alcohol loading down-regulates hepatic hepcidin expression and leads to the increase of iron absorption from the intestine.
Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Hemossiderose/genética , Sobrecarga de Ferro/genética , Hepatopatias Alcoólicas/genética , Animais , Peptídeos Catiônicos Antimicrobianos/sangue , Regulação para Baixo/genética , Ferritinas/sangue , Hemossiderose/sangue , Hemossiderose/patologia , Hepcidinas , Humanos , Absorção Intestinal/genética , Ferro/sangue , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/patologia , Fígado/metabolismo , Hepatopatias Alcoólicas/sangue , Hepatopatias Alcoólicas/patologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Precursores de Proteínas/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The present study was performed to examine a hypothesis that peroxisome proliferator-activated receptor gamma (PPARgamma) is implicated in high fat diet-induced liver steatosis. Mice were fed with control or high fat diet containing approximately 10% or 80% cholesterol, respectively. Macroscopic and microscopic findings demonstrated that lipid accumulation in the liver was observed as early as 2 weeks after high fat diet and that high fat diet for 12 weeks developed a fatty liver phenotype, establishing a novel model of diet-induced liver steatosis. Gene profiling with microarray and real-time PCR studies demonstrated that among genes involved in lipid metabolism, adipogenesis-related genes, PPARgamma and its targeted gene, CD36 mRNA expression was specifically up-regulated in the liver by high fat diet for 2 weeks. Immunohistochemical study revealed that PPARgamma protein expression is increased in the nuclei of hepatocytes by high fat diet. It was also shown that protein expression of cAMP response element-binding protein (CREB), an upstream molecule of PPARgamma, in the liver was drastically suppressed by high fat diet. All these results suggest for the first time that the CREB-PPARgamma signaling pathway may be involved in the high fat diet-induced liver steatosis.
