Suppression of Aquaporin Adipose Gene Expression by Isoproterenol, TNFα, and Dexamethasone

Abstract

Aquaporin adipose (AQPap) is a putative glycerol channel in adipocytes. It has recently been shown to be upregulated in insulin resistance stimulated by thiazolidinediones and inhibited by insulin. To further clarify regulation of AQPap gene expression, 3T3-L1 adipocytes were chronically treated with various hormones known to influence insulin sensitivity and adipocyte metabolism, and AQPap mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, treatment of 3T3-Ll adipocytes with 10 µM isoproterenol, 10 ng/ml TNFα, and 100 nM dexamethasone for 16 h inhibited AQPap gene expression by 62 %, 60 %, and 39 %, respectively; angiotensin 2, growth hormone, and triiodothyronine did not have any effect. The inhibitory effects were dose-dependent with significant suppression detectable at concentrations as low as 1 nM isoproterenol, 1 ng/ml TNFα, and 10 nM dexamethasone. Furthermore, inhibition of AQPap gene expression could be almost completely reversed by pretreating 3T3-L1 adipocytes with the β-adrenoceptor antagonist propranolol. Moreover, stimulation of Gs-proteins with cholera toxin and adenylyl cyclase with forskolin and dibutyryl-cAMP dramatically downregulated AQPap mRNA. Taken together, our results suggest that AQPap is an adipocyte-expressed glycerol channel selectively regulated and profoundly downregulated by hormones implicated in the pathogenesis of insulin resistance and dyslipidemia.

Key words

3T3-L1 adipocyte - AQPap - Glycerol channel - Insulin resistance - Obesity

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