| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print November 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
agonist rosiglitazone
* Lipomics Technologies, Inc., 2545 Boatman Ave., West Sacramento, CA 95691
The Jackson Laboratory, 600 Main St., Bar Harbor, ME
Department of Food Science & Technology, University of California, Davis, CA
1 To whom correspondence should be addressed. e-mail: steve.watkins{at}lipomics.com
Successful therapy for chronic diseases must normalize a targeted aspect of metabolism without disrupting the regulation of other metabolic pathways essential for maintaining health. Use of a limited number of single molecule surrogates for disease, or biomarkers, to monitor the efficacy of a therapy may fail to predict undesirable side effects. In this study, a comprehensive metabolomic assessment of lipid metabolites was employed to determine the specific effects of the peroxisome proliferator-activated receptor 
(PPAR) agonist rosiglitazone on structural lipid metabolism in a new mouse model of Type 2 diabetes. Dietary supplementation with rosiglitazone (200 mg/kg diet) suppressed Type 2 diabetes in obese (NZO x NON)F1 male mice, but chronic treatment markedly exacerbated hepatic steatosis. The metabolomic data revealed that rosiglitazone i) induced hypolipidemia (by dysregulating liver–plasma lipid exchange), ii) induced de novo fatty acid synthesis, iii) decreased the biosynthesis of lipids within the peroxisome, iv) substantially altered free fatty acid and cardiolipin metabolism in heart, and v) elicited an unusual accumulation of polyunsaturated fatty acids within adipose tissue. These observations suggest that the phenotypes induced by rosiglitazone are mediated by multiple tissue-specific metabolic variables.
Because many of the effects of rosiglitazone on tissue metabolism were reflected in the plasma lipid metabolome, metabolomics has excellent potential for developing clinical assessments of metabolic response to drug therapy.
Abbreviations: PPAR, peroxisome proliferator-activated receptor ; TZD, thiazolidinedione
Supplementary key words diabetes • lipid metabolism • metabolomics • steatosis • peroxisome proliferator-activated receptor • mouse
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. L. Griffin and A. Vidal-Puig Current challenges in metabolomics for diabetes research: a vital functional genomic tool or just a ploy for gaining funding? Physiol Genomics, June 10, 2008; 34(1): 1 - 5. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Benton, G. P. Holloway, S. E. Campbell, Y. Yoshida, N. N. Tandon, J. F. C. Glatz, J. J. J. F. P. Luiken, L. L. Spriet, and A. Bonen Rosiglitazone increases fatty acid oxidation and fatty acid translocase (FAT/CD36) but not carnitine palmitoyltransferase I in rat muscle mitochondria J. Physiol., March 15, 2008; 586(6): 1755 - 1766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Astle, J. T. Ferguson, J. B. German, G. G. Harrigan, N. L. Kelleher, T. Kodadek, B. A. Parks, M. J. Roth, K. W. Singletary, C. D. Wenger, et al. Characterization of Proteomic and Metabolomic Responses to Dietary Factors and Supplements J. Nutr., December 1, 2007; 137(12): 2787 - 2793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Waites, M. A. Dominick, T. P. Sanderson, and B. E. Schilling Nonclinical Safety Evaluation of Muraglitazar, a Novel PPAR{alpha}/{gamma} Agonist Toxicol. Sci., November 1, 2007; 100(1): 248 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Walzem, R. A. Baillie, M. Wiest, R. Davis, S. M. Watkins, T. E. Porter, J. Simon, and L. A. Cogburn Functional Annotation of Genomic Data with Metabolic Inference Poult. Sci., July 1, 2007; 86(7): 1510 - 1522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Morehouse, E. D. Sugarman, P.-A. Bourassa, T. M. Sand, F. Zimetti, F. Gao, G. H. Rothblat, and A. J. Milici Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits J. Lipid Res., June 1, 2007; 48(6): 1263 - 1272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Rizki, L. Arnaboldi, B. Gabrielli, J. Yan, G. S. Lee, R. K. Ng, S. M. Turner, T. M. Badger, R. E. Pitas, and J. J. Maher Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1 J. Lipid Res., October 1, 2006; 47(10): 2280 - 2290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Shulaev Metabolomics technology and bioinformatics Brief Bioinform, June 1, 2006; 7(2): 128 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Leiter, P. C. Reifsnyder, W. Zhang, H.-j. Pan, Q. Xiao, and J. Mistry Differential Endocrine Responses to Rosiglitazone Therapy in New Mouse Models of Type 2 Diabetes Endocrinology, February 1, 2006; 147(2): 919 - 926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Ginsburg, M. P. Donahue, and L. K. Newby Prospects for Personalized Cardiovascular Medicine: The Impact of Genomics J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1615 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Mutch, W. Wahli, and G. Williamson Nutrigenomics and nutrigenetics: the emerging faces of nutrition FASEB J, October 1, 2005; 19(12): 1602 - 1616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J Gibney, M. Walsh, L. Brennan, H. M Roche, B. German, and B. van Ommen Metabolomics in human nutrition: opportunities and challenges Am. J. Clinical Nutrition, September 1, 2005; 82(3): 497 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Pan, P. Reifsnyder, D. E. Vance, Q. Xiao, and E. H. Leiter Pharmacogenetic Analysis of Rosiglitazone-Induced Hepatosteatosis in New Mouse Models of Type 2 Diabetes Diabetes, June 1, 2005; 54(6): 1854 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Makowski, K. C. Brittingham, J. M. Reynolds, J. Suttles, and G. S. Hotamisligil The Fatty Acid-binding Protein, aP2, Coordinates Macrophage Cholesterol Trafficking and Inflammatory Activity: MACROPHAGE EXPRESSION OF aP2 IMPACTS PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR {gamma} AND I{kappa}B KINASE ACTIVITIES J. Biol. Chem., April 1, 2005; 280(13): 12888 - 12895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Wu, H. Hyogo, S. K. Yadav, P. M. Novikoff, and D. E. Cohen Impaired response of biliary lipid secretion to a lithogenic diet in phosphatidylcholine transfer protein-deficient mice J. Lipid Res., March 1, 2005; 46(3): 422 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Bruder, P. C. Lee, and H. Raff Dexamethasone treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids J Appl Physiol, March 1, 2005; 98(3): 981 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Bruder, P. C. Lee, and H. Raff Metabolic Consequences of Hypoxia from Birth and Dexamethasone Treatment in the Neonatal Rat: Comprehensive Hepatic Lipid and Fatty Acid Profiling Endocrinology, November 1, 2004; 145(11): 5364 - 5372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ghazalpour, S. Doss, X. Yang, J. Aten, E. M. Toomey, A. Van Nas, S. Wang, T. A. Drake, and A. J. Lusis Thematic review series: The Pathogenesis of Atherosclerosis. Toward a biological network for atherosclerosis J. Lipid Res., October 1, 2004; 45(10): 1793 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. German, D. E. Bauman, D. G. Burrin, M. L. Failla, H. C. Freake, J. C. King, S. Klein, J. A. Milner, G. H. Pelto, K. M. Rasmussen, et al. Metabolomics in the Opening Decade of the 21st Century: Building the Roads to Individualized Health J. Nutr., October 1, 2004; 134(10): 2729 - 2732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J B. German and C. J Dillard Saturated fats: what dietary intake? Am. J. Clinical Nutrition, September 1, 2004; 80(3): 550 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Milner Molecular Targets for Bioactive Food Components J. Nutr., September 1, 2004; 134(9): 2492S - 2498S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tiikkainen, A.-M. Hakkinen, E. Korsheninnikova, T. Nyman, S. Makimattila, and H. Yki-Jarvinen Effects of Rosiglitazone and Metformin on Liver Fat Content, Hepatic Insulin Resistance, Insulin Clearance, and Gene Expression in Adipose Tissue in Patients With Type 2 Diabetes Diabetes, August 1, 2004; 53(8): 2169 - 2176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Maruvada and S. Srivastava Biomarkers for Cancer Diagnosis: Implications for Nutritional Research J. Nutr., June 1, 2004; 134(6): 1640S - 1645S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Bruder, P. C. Lee, and H. Raff Metabolomic analysis of adrenal lipids during hypoxia in the neonatal rat: implications in steroidogenesis Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E697 - E703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Leiter and P. C. Reifsnyder Differential Levels of Diabetogenic Stress in Two New Mouse Models of Obesity and Type 2 Diabetes Diabetes, February 1, 2004; 53(90001): S4 - 11. [Abstract] [Full Text]
|
|
|
|
|
|
J. B. German, M.-A. Roberts, and S. M. Watkins Personal Metabolomics as a Next Generation Nutritional Assessment J. Nutr., December 1, 2003; 133(12): 4260 - 4266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Watkins, X. Zhu, and S. H. Zeisel Phosphatidylethanolamine-N-methyltransferase Activity and Dietary Choline Regulate Liver-Plasma Lipid Flux and Essential Fatty Acid Metabolism in Mice J. Nutr., November 1, 2003; 133(11): 3386 - 3391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. German, M.-A. Roberts, and S. M. Watkins Genomics and Metabolomics as Markers for the Interaction of Diet and Health: Lessons from Lipids J. Nutr., June 1, 2003; 133(6): 2078S - 2083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Noguchi, R. Sakai, and T. Kimura Metabolomics and its Potential for Assessment of Adequacy and Safety of Amino Acid Intake J. Nutr., June 1, 2003; 133(6): 2097S - 2100. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
