Читать книгу Drug Transporters - Группа авторов - Страница 98

Nonalcoholic fatty liver disease is a prevalent disease in the US patients with advanced disease, or steatohepatitis, often have comorbidities such as type II diabetes and chronic kidney disease. Pathologic features of nonalcoholic steatohepatitis can be recapitulated by feeding rodents a diet deficient in methionine and choline (MCD) or in mice with a genetic predisposition for obesity (known as ob/ob mice). Expression of mOct2 and mMate1 mRNA is reduced in the kidneys of ob/ob mice [85]. Feeding ob/ob mice a MCD diet further lowered expression of mOct2 and mMate1 in the kidneys, which was associated with impaired clearance of metformin. Interestingly, changes in mOct1 or mMate1 mRNA expression were observed in the livers of ob/ob mice regardless of diet [85]. Emerging data from humans with nonalcoholic steatohepatitis or untreated type II diabetes demonstrate hypermethylation of the SLC47A1 gene in liver [86, 87]. These data would tend to support decreased hMATE1 expression as methylation status is a contributor to the interindividual regulation of hMATE1 [88].