RESUMO
Non-alcoholic fatty liver disease (NAFLD) can progress from steatosis to non-alcoholic steatohepatitis (NASH) characterized by liver inflammation, possibly leading to cirrhosis and hepatocellular carcinoma (HCC). Mice with impaired macrophage activation, when fed a high-fat diet, develop severe NASH. Evidence is mounting that Kupffer cells are implicated. However, it is unknown whether the resident CD68+ or bone marrow-derived CD11b+ Kupffer cells are involved. Characterization of the FSP1cre-Pparb/d-/- mouse liver revealed that FSP1 is expressed in CD11b+ Kupffer cells. Although these cells only constitute a minute fraction of the liver cell population, Pparb/d deletion in these cells led to remarkable hepatic phenotypic changes. We report that a higher lipid content was present in postnatal day 2 (P2) FSP1cre-Pparb/d-/- livers, which diminished after weaning. Quantification of total lipids and triglycerides revealed that P2 and week 4 of age FSP1cre-Pparb/d-/- livers have higher levels of both. qPCR analysis also showed upregulation of genes involved in fatty acid ß-oxidation, and fatty acid and triglyceride synthesis pathways. This result is further supported by western blot analysis of proteins in these pathways. Hence, we propose that FSP1cre-Pparb/d-/- mice, which accumulate lipids in their liver in early life, may represent a useful animal model to study juvenile NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR beta/genética , Proteína A4 de Ligação a Cálcio da Família S100/genética , Animais , Biomarcadores , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Hepatócitos/metabolismo , Espaço Intracelular/metabolismo , Células de Kupffer/metabolismo , Metabolismo dos Lipídeos , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Oxirredução , PPAR beta/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/metabolismoRESUMO
Objective To explore the change of the activities of peroxisome ?-oxidation in T2DM patients with the lipid disorders.Methods We analyzed the changes of the activities of peroxisome ?-oxidation and fatty acyl-CoA oxidase and its mRNA expression in 112 cases of T2DM patients.Results We found that there was compensatory increase in activity of peroxisome ?-oxidation of T2DM patients.As compared with control group,the activity of fatty acyl-CoA oxidase of T2DM group was increased by 5%(P