title: Deletion of glycerol channel aquaporin-9 (Aqp9) impairs long-term blood glucose control in C57BL/6 leptin receptor-deficient (db/db) obese mice.
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.
authors.affiliation: Unit of Molecular Metabolism, Lund University Diabetes Centre CRC Skåne University Hospital, Malmö, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Spegel
authors.affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.
authors.forename: Aakash
authors.initials: A
authors.lastname: Chawade
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.affiliation: Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Kjellbom
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden miru@hst.aau.dk.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0001-5597-8880
authors.initials: M
authors.lastname: Rützler
keywords: Nt5e; aquaporin‐9; atherosclerosis; branched chain ketoacid dehydrogenase; metabolomics