Multi-platform investigation of the metabolome in a leptin receptor defective murine model of type 2 diabetes

Gipson, Geoffrey T., Tatsuoka, Kay S., Ball, Rachel J., Sokhansanj, Bahrad A., Hansen, Michael K., Ryan, Terence E., Hodson, Mark P., Sweatman, Brian C. and Connor, Susan C. (2008) Multi-platform investigation of the metabolome in a leptin receptor defective murine model of type 2 diabetes. Molecular Biosystems, 4 10: 1015-1023. doi:10.1039/b807332e


Author Gipson, Geoffrey T.
Tatsuoka, Kay S.
Ball, Rachel J.
Sokhansanj, Bahrad A.
Hansen, Michael K.
Ryan, Terence E.
Hodson, Mark P.
Sweatman, Brian C.
Connor, Susan C.
Title Multi-platform investigation of the metabolome in a leptin receptor defective murine model of type 2 diabetes
Journal name Molecular Biosystems   Check publisher's open access policy
ISSN 1742-206X
1742-2051
Publication date 2008-08-07
Sub-type Article (original research)
DOI 10.1039/b807332e
Open Access Status Not Open Access
Volume 4
Issue 10
Start page 1015
End page 1023
Total pages 9
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Language eng
Formatted abstract
We describe a multi-platform (1H NMR, LC-MS, microarray) investigation of metabolic disturbances associated with the leptinreceptor defective (db/db) mouse model of type 2 diabetes using novel assignment methodologies. For the first time, several urinary metabolites were found to be associated with diabetes and/or diabetes progression and confirmed in both NMR and LC-MS datasets. The confirmed metabolites were trimethylamine-n-oxide (TMAO), creatine, carnitine, and phenylalanine. TMAO and phenylalanine were both elevated in db/db mice and decreased in these mice with age. Levels of both creatine and carnitine increase in diabetic mice with age and creatine was also significantly decreased in db/db mice. Additionally, many metabolic markers were found by either NMR or LC-MS, but could not be found in both, due to instrumental limitations. This indicates that the combined use of NMR and LC-MS instrumentation provides complementary information that would be otherwise unattainable. Pathway analyses of urinary metabolites and liver, muscle, and adipose tissue transcripts from the db/db model were also performed to identify altered biochemical processes in the diabetic mice. Metabolite and liver transcript levels associated with the TCA cycle and steroid processes were altered in db/db mice. In addition, gene expression in muscle and liver associated with fatty acid processing was altered in the diabetic mice and similar evidence was observed in the LC-MS data. Our findings highlight the importance of a number of processes known to be associated with diabetes and reveal tissue specific responses to the condition. When studying metabolic disorders such as diabetes, multiple platform integrated profiling of metabolite alterations in biofluids can provide important insights into the processes underlying the disease.
© Royal Society of Chemistry 2011
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
 
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Created: Fri, 03 Jun 2011, 14:08:10 EST by Dr Mark Hodson on behalf of Aust Institute for Bioengineering & Nanotechnology