Effects of obesity on the hepatic expression of organic cation transporter 1 (SLC22A1)

초록

Organic cation transporter 1 (OCT1/SLC22A1) is a member of solute carrier (SLC) transporters responsible, at least in part, for the uptake of organic cations, including xenobiotics and endogenous compounds. OCT1 constitutes an important factor in the hepatic distribution of drugs, such as metformin. Although it was known that various factors influence on the expression of OCT1, it has been not known the effects of obesity on the expression of hepatic OCT1. Here, we measured the hepatic expression of OCT1 in animal models of diet-induced obesity (DIO). Furthemore, we determined the hepatic distribution of a substrate drug, metformin. High-fat diet-induced obesity (HF-DIO) in C57/Bl6 mice was induced by HF diet containing 40% beef tallow for 19 weeks. Lean control mice were fed with control chow diet. In high-fat diet-induced obese mice, the hepatic expressions of OCT1 mRNA and protein were higher (1.2~1.3 folds) as compared with lean control mice (p < 0.05). Consistently, the extent of hepatic distribution of metformin in HF-DIO mice was higher (~ 2 folds) than that in matched lean mice (p < 0.001). In conclusion, obesity increases the hepatic expression of OCT1 and subsequent hepatic distribution of substrate drug