Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, 7 Greenhouse Road, Kingston, Rhode Island, 02881, USA.
Pharm Res. 2013 Sep;30(9):2232-47. doi: 10.1007/s11095-013-1140-2. Epub 2013 Aug 16.
Fatty liver alters liver transporter expression. Caloric restriction (CR), the recommended therapy to reverse fatty liver, increases Sirtuin1 deacetylase activity in liver. This study evaluated whether CR and CR mimetics reversed obesity-induced transporter expression in liver and hepatocytes.
mRNA and protein expression was determined in adult lean (lean) and leptin-deficient obese (OB) mice fed ad libitum or placed on 40% (kCal) reduced diet. Hepatocytes were isolated from lean and OB mice, treated with AMP Kinase activators, and gene expression was determined.
CR decreased Oatp1a1, Oatp1b2, and Abcb11 mRNA expression in lean, but not OB mice. CR increased Abcc2 mRNA OB livers, whereas protein expression increased in both genotypes. CR increased Abcc3 protein expression increased in OB livers. CR did not alter Abcc1, 4 and 5 mRNA expression in lean mice but decreased expression in livers of OB mice. CR increased Abcc4 protein in lean, but not OB mice.
CR restriction reversed the expression of some, but not all transporters in livers of OB mice. Overall, these data indicate a potential for CR to restore some hepatic transporter changes in OB mice, but suggest a functional leptin axis is needed for reversal of expression for some transporters.
脂肪肝改变肝脏转运蛋白的表达。热量限制（CR）是逆转脂肪肝的推荐疗法，可增加肝脏中的 Sirtuin1 去乙酰化酶活性。本研究评估了 CR 和 CR 模拟物是否能逆转肥胖引起的肝脏和肝细胞转运蛋白表达。
在自由进食的成年瘦（瘦）和瘦素缺乏肥胖（OB）小鼠或给予 40%（卡路里）减少饮食的肥胖小鼠中测定 mRNA 和蛋白表达。从瘦鼠和 OB 鼠中分离肝细胞，用 AMP 激酶激活剂处理，并测定基因表达。
CR 降低了 lean 小鼠但不降低 OB 小鼠中 Oatp1a1、Oatp1b2 和 Abcb11 的 mRNA 表达。CR 增加了 OB 肝脏中的 Abcc2 mRNA，而两种基因型的蛋白表达均增加。CR 增加了 OB 肝脏中 Abcc3 蛋白的表达。CR 未改变 lean 小鼠中 Abcc1、4 和 5 的 mRNA 表达，但降低了 OB 小鼠肝脏中的表达。CR 增加了 lean 小鼠的 Abcc4 蛋白，但不增加 OB 小鼠的 Abcc4 蛋白。
CR 限制逆转了 OB 小鼠肝脏中一些但不是所有转运蛋白的表达。总体而言，这些数据表明 CR 有可能恢复 OB 小鼠肝脏中一些转运蛋白的变化，但提示需要功能性瘦素轴来逆转某些转运蛋白的表达。
