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

Spégel, Peter LU ; Chawade, Aakash LU ; Nielsen, Søren ; Kjellbom, Per LU and Rützler, Michael LU (2015) In Physiological Reports 3(9).
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... (More)
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. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physiological Reports
volume
3
issue
9
article number
e12538
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:26416971
  • pmid:26416971
  • scopus:84949836538
  • wos:000214778200028
ISSN
2051-817X
DOI
10.14814/phy2.12538
language
English
LU publication?
yes
id
bf6e35da-a5de-42f8-a967-d860cad3b86f (old id 8034565)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26416971?dopt=Abstract
date added to LUP
2016-04-04 09:04:26
date last changed
2022-03-15 17:32:33
@article{bf6e35da-a5de-42f8-a967-d860cad3b86f,
  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 &lt; 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.}},
  author       = {{Spégel, Peter and Chawade, Aakash and Nielsen, Søren and Kjellbom, Per and Rützler, Michael}},
  issn         = {{2051-817X}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Physiological Reports}},
  title        = {{Deletion of glycerol channel aquaporin-9 (Aqp9) impairs long-term blood glucose control in C57BL/6 leptin receptor-deficient (db/db) obese mice.}},
  url          = {{http://dx.doi.org/10.14814/phy2.12538}},
  doi          = {{10.14814/phy2.12538}},
  volume       = {{3}},
  year         = {{2015}},
}