Regulation of adipocyte differentiation and metabolism by lansoprazole

LIFE SCIENCES

卷:239

Article

Benchamana, Ameena^1,3  Mori, Hiroyuki³  MacDougald, Ormond A.³  Soodvilai, Sunhapas^1,2 

[1] Mahidol Univ, Fac Sci, Dept Physiol, Res Ctr Transport Prot Med Innovat, Bangkok, Thailand

[2] Mahidol Univ, Fac Sci, ECDD, Bangkok, Thailand

[3] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI USA

关键词: Lansoprazole;    Anti-diabetic;    Adipogenesis;    Proton pump inhibitor;   

DOI  :  10.1016/j.lfs.2019.116897

来源: Elsevier

【 摘 要 】

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 PPAR gamma and C/EBP alpha, 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 PPAR gamma and C/EBP alpha, and maintained expression of preadipocytes markers, beta-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 PPAR gamma and C/EBP alpha.

【 授权许可】

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