Deletion of glycerol channel aquaporin‐9 (Aqp9) impairs long‐term blood glucose control in C57BL/6 leptin receptor–deficient (db/db) obese mice

Physiological Reports

Peter Spegel⁴  Aakash Chawade¹  Søren Nielsen³  Per Kjellbom² 

[1] Department of Immunotechnology, Lund University, Lund, Sweden;Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden;Department of Health Science and Technology, Aalborg University, Aalborg, Denmark;Unit of Molecular Metabolism, Lund University Diabetes Centre, CRC, Skåne University Hospital, Malmö, Sweden

关键词: aquaporin‐9;    atherosclerosis;    branched chain ketoacid dehydrogenase;    metabolomics;    Nt5e;   

DOI  :  10.14814/phy2.12538

来源: Wiley

【 摘 要 】

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. Aqp9^wt 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 Aqp9^wt 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.

【 授权许可】

CC BY   
© 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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