Ameena Benchamana1, Hiroyuki Mori2, Ormond A MacDougald2, Sunhapas Soodvilai3. 1. Research Center of Transport Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, USA. 2. University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, USA. 3. Research Center of Transport Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address: sunhapas.soo@mahidol.ac.th.
Abstract
AIMS: Lansoprazole (LPZ) is one of the most commonly prescribed drugs for treatment of acid-related diseases, and it is increasingly recognized for its potential application as an anti-diabetic therapy. Although LPZ target tissues remain poorly understood, possible sites of action include adipose tissue. In this study, we assessed effects of LPZ on adipocyte differentiation and function by using 3T3-L1 preadipocytes and HFD-induced obesity mice as an in vitro and in vivo model, respectively. MAIN METHODS: Oil red O staining and intracellular triacylglycerol content were used to determine lipid accumulation. Glucose uptake was performed to measure mature adipocyte function. Expression of adipocyte genes was determined by qRT-PCR and immunoblotting. KEY FINDINGS: LPZ has dual effects on differentiation of 3T3-L1 cells. At low concentrations, LPZ enhanced adipocyte differentiation via induction of PPARγ and C/EBPα, two master adipogenic transcription factors, as well as lipogenic proteins, ACC1 and FASN. Increasing of adipocyte number subsequently increased basal and insulin-stimulated glucose uptake, and expression of Glut4 mRNA. Conversely, high concentrations of LPZ strongly inhibited differentiation and expression of PPARγ and C/EBPα, and maintained expression of preadipocytes markers, β-catenin and Pref-1. Inhibition of adipogenesis by LPZ reduced mature adipocyte number, Glut4 mRNA expression and insulin-stimulated glucose uptake. In addition, treatment with LPZ at 200 mg/kg significantly reduced body weight gain and total fat mass in HFD-induced obese mice. SIGNIFICANCE: These results indicate that effects of LPZ on adipocyte differentiation are dependent on concentration and are correlated with PPARγ and C/EBPα.
AIMS: Lansoprazole (LPZ) is one of the most commonly prescribed drugs for treatment of acid-related diseases, and it is increasingly recognized for its potential application as an anti-diabetic therapy. Although LPZ target tissues remain poorly understood, possible sites of action include adipose tissue. In this study, we assessed effects of LPZ on adipocyte differentiation and function by using 3T3-L1 preadipocytes and HFD-induced obesitymice as an in vitro and in vivo model, respectively. MAIN METHODS:Oil red O staining and intracellular triacylglycerol content were used to determine lipid accumulation. Glucose uptake was performed to measure mature adipocyte function. Expression of adipocyte genes was determined by qRT-PCR and immunoblotting. KEY FINDINGS:LPZ has dual effects on differentiation of 3T3-L1 cells. At low concentrations, LPZ enhanced adipocyte differentiation via induction of PPARγ and C/EBPα, two master adipogenic transcription factors, as well as lipogenic proteins, ACC1 and FASN. Increasing of adipocyte number subsequently increased basal and insulin-stimulated glucose uptake, and expression of Glut4 mRNA. Conversely, high concentrations of LPZ strongly inhibited differentiation and expression of PPARγ and C/EBPα, and maintained expression of preadipocytes markers, β-catenin and Pref-1. Inhibition of adipogenesis by LPZ reduced mature adipocyte number, Glut4 mRNA expression and insulin-stimulated glucose uptake. In addition, treatment with LPZ at 200 mg/kg significantly reduced body weight gain and total fat mass in HFD-induced obesemice. SIGNIFICANCE: These results indicate that effects of LPZ on adipocyte differentiation are dependent on concentration and are correlated with PPARγ and C/EBPα.
Authors: Karin D Hove; Kristine Færch; Thóra B Bödvarsdóttir; Allan E Karlsen; Jacob S Petersen; Allan Vaag Journal: Diabetes Res Clin Pract Date: 2010-12 Impact factor: 5.602
Authors: Cheng Xiao; Hai Guo Jin; Li Chun Zhang; Jian Qiang Liu; Ming He; Hui Hai Ma; Yong Sheng Yu; Yang Cao Journal: Adipocyte Date: 2021-12 Impact factor: 4.534