Chaoyu Zhu1, Yuanyuan Xiao, Xiaohua Liu, Junfeng Han, Jianmei Zhang, Li Wei, Weiping Jia. 1. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai, China.
Abstract
BACKGROUND/AIMS: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4), an adipocytokine associated with obesity and insulin resistance. METHODS: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. RESULTS: Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. CONCLUSION: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.
BACKGROUND/AIMS: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4), an adipocytokine associated with obesity and insulin resistance. METHODS: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. RESULTS:Pioglitazone treatment significantly decreased serum RBP4 levels in obeserats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. CONCLUSION: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obeserats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.
Authors: Jaclyn E Welles; Allyson L Toro; Siddharth Sunilkumar; Shaunaci A Stevens; Carson J Purnell; Scot R Kimball; Michael D Dennis Journal: Am J Physiol Endocrinol Metab Date: 2020-12-07 Impact factor: 4.310
Authors: Ali Saeed; Joanne A Hoogerland; Hanna Wessel; Janette Heegsma; Terry G J Derks; Eveline van der Veer; Gilles Mithieux; Fabienne Rajas; Maaike H Oosterveer; Klaas Nico Faber Journal: Hum Mol Genet Date: 2020-01-15 Impact factor: 6.150