Abstract
Deletion of the glycerol channel aquaporin-9 (Aqp9) reduces postprandial blood glucose levels in leptin receptor–deficient (db/db) obese mice on a C57BL/6 × C57BLKS mixed genetic background. Furthermore, shRNA-mediated reduction of Aqp9 expression reduces liver triacylglycerol (TAG) accumulation in a diet-induced rat model of obesity. The aim of this study was to investigate metabolic effects of Aqp9 deletion in coisogenic db/db mice of the C57BL/6 background. Aqp9wt db/db and Aqp9−/− db/db mice did not differ in body weight and liver TAG contents. On the C57BL/6 genetic background, we observed elevated plasma glucose in Aqp9−/− db/db mice (+1.1 mmol/L, life-time average), while plasma insulin concentration was reduced at the time of death. Glucose levels changed similarly in pentobarbital anesthetized, glucagon challenged Aqp9wt db/db and Aqp9−/− db/db mice. Liver transcriptional profiling did not detect differential gene expression between genotypes. Metabolite profiling revealed a sex independent increase in plasma glycerol (+55%) and glucose (+24%), and reduction in threonate (all at q < 0.1) in Aqp9−/− db/db mice compared to controls. Metabolite profiling thus confirms a role of AQP9 in glycerol metabolism of obese C57BL/6 db/db mice. In this animal model of obesity Aqp9 gene deletion elevates plasma glucose and does not alleviate hepatosteatosis.
Highlights
Aquaporin-9 (AQP9), a member of the major intrinsic protein family of transmembrane channels is permeable to glycerol, urea, and some other small, neutral solutes (Tsukaguchi et al 1998)
In order to investigate the role of AQP9 in coisogenic C57BL/6 db/db mice we crossed the original C57BL/6 Aqp9À/À strain (Rojek et al 2007) with C57BL/6 db/db mice and monitored body weight and blood glucose of F2 generation mice, between 6 and 18 weeks of age
Fasted blood glucose levels tended to be higher in Aqp9À/À than in Aqp9wt mice on the C57BL/6 db/db genetic background (Fig. 1B), which contrasts previous observations in C57BL/6 9 C57BLKS mice (Rojek et al 2007)
Summary
Aquaporin-9 (AQP9), a member of the major intrinsic protein family of transmembrane channels is permeable to glycerol, urea, and some other small, neutral solutes (Tsukaguchi et al 1998). Aqp gene deletion results in elevated plasma glycerol levels (Rojek et al 2007). AQP9 expression is enhanced by prolonged fasting (Kuriyama et al 2002; Calamita et al 2012), whereby elevation in protein levels has been found in male mice a 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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