AJP - Endo Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 292: E1157-E1165, 2007. First published December 12, 2006; doi:10.1152/ajpendo.00254.2006
0193-1849/07 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
292/4/E1157    most recent
00254.2006v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (6)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sheikh, K.
Right arrow Articles by Oakes, N. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sheikh, K.
Right arrow Articles by Oakes, N. D.

Beyond lipids, pharmacological PPAR{alpha} activation has important effects on amino acid metabolism as studied in the rat

Kashif Sheikh, Germán Camejo, Boel Lanne, Torbjörn Halvarsson, Marie Rydén Landergren, and Nicholas D. Oakes

AstraZeneca R&D Cardiovascular/Gastrointestinal, Mölndal, Sweden

Submitted 26 May 2006 ; accepted in final form 11 December 2006

PPAR{alpha} agonists have been characterized largely in terms of their effects on lipids and glucose metabolism, whereas little has been reported about effects on amino acid metabolism. We studied responses to the PPAR{alpha} agonist WY 14,643 (30 µmol·kg–1·day–1 for 4 wk) in rats fed a saturated fat diet. Plasma and urine were analyzed with proton NMR. Plasma amino acids were measured using HPLC, and hepatic gene expression was assessed with DNA arrays. The high-fat diet elevated plasma levels of insulin and triglycerides (TG), and WY 14,643 treatment ameliorated this insulin resistance and dyslipidemia, lowering plasma insulin and TG levels. In addition, treatment decreased body weight gain, without altering cumulative food intake, and increased liver mass. WY 14,643 increased plasma levels of 12 of 22 amino acids, including glucogenic and some ketogenic amino acids, whereas arginine was significantly decreased. There was no alteration in branched-chain amino acid levels. Compared with the fat-fed control animals, WY 14,643-treated animals had raised plasma urea and ammonia levels as well as raised urine levels of N-methylnicotinamide and dimethylglycine. WY 14,643 induced changes in a number of key genes involved in amino acid metabolism in addition to expected effects on hepatic genes involved in lipid catabolism and ketone body formation. In conclusion, the present results suggest that, in rodents, effects of pharmacological PPAR{alpha} activation extend beyond control of lipid metabolism to include important effects on whole body amino acid mobilization and hepatic amino acid metabolism.

peroxisome proliferator-activated receptor-{alpha}


Address for reprint requests and other correspondence: Nick Oakes, AstraZeneca R&D Mölndal, S-431 83, Mölndal, Sweden (e-mail: nick.oakes{at}astrazeneca.com)




This article has been cited by other articles:


Home page
 FASEB J.Home page
L. Makowski, R. C. Noland, T. R. Koves, W. Xing, O. R. Ilkayeva, M. J. Muehlbauer, R. D. Stevens, and D. M. Muoio
Metabolic profiling of PPAR{alpha}-/- mice reveals defects in carnitine and amino acid homeostasis that are partially reversed by oral carnitine supplementation
FASEB J, February 1, 2009; 23(2): 586 - 604.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.