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Investigation of the regulation of adipose ADMA during weight change. (360G-Wellcome-078055_Z_05_Z)

Signals from adipose tissue may underlie the relationship between obesity and metabolic diseases through their effects on insulin sensitivity and endothelial function. Asymmetric dimethylarginine (ADMA) is a novel risk factor for cardiovascular disease that inhibits nitric oxide bioavailability and causes endothelial dysfunction. ADMA is primarily cleared by catabolism through the activity of dimethylarginine dimethylaminohydrolase (DDAH). We found that adipose tissue expresses DDAH to high levels and generates significant amounts of ADMA, and the release is modifiable by changes in weight and insulin sensitizers. We propose to investigate the ADMA/DDAH pathway in adipose tissue of DDAH-1 +/- mice, and their wild-type littermates,to explore its relationship to the development of endothelial dysfunction in diet-induced obesity and to assess the reversibility of these changes by weight loss. Adipose tissue distribution and detailed quantification of changes in energy expenditure will be determined, as well as organ cultures toevaluate adipose ADMA secretion. Understanding the effects of the dynamic changes in weight on the adipose tissue DDAH/ADMA pathway and its regulation will increase our understanding of this novel product of this organ, explain the close link between body fat and endothelial dysfunction and provide a valuable basis for designing strategies in the treatment of obesity-associatedpathologies.


07 Nov 2005

Grant details
Amount Awarded 236395
Applicant Surname Mohamed-Ali
Approval Committee Physiological Sciences Funding Committee
Award Date 2005-11-07T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Project Grant
Internal ID 078055/Z/05/Z
Lead Applicant Dr Vidya Mohamed-Ali
Other Applicant(s) Dr James Leiper, Prof John Speakman, Prof Patrick Vallance
Planned Dates: End Date 2009-02-12T00:00:00+00:00
Planned Dates: Start Date 2006-02-13T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
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