Diabetes, Vol 47, Issue 9 1451-1458, Copyright © 1998 by American Diabetes Association

ARTICLES

Alterations in skeletal muscle gene expression of ob/ob mice by mRNA differential display

D Vicent, M Piper, S Gammeltoft, E Maratos-Flier and CR Kahn
Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.

To identify molecules that contribute to insulin resistance, we compared the patterns of gene expression in skeletal muscle of the obese ob/ob mouse, a genetic model of obesity and severe insulin resistance, with that of its thin littermate (ob/+) using the mRNA differential display method. From about 9,000 cDNAs displayed, we found 12 differentially expressed in ob/ob mice skeletal muscle that could be recovered from the differential display gels and confirmed by Northern blot analysis and sequenced. Eight mRNAs were overexpressed in ob/ob muscle: Id2 (a negative regulator of the basic helix-loop-helix family of transcription factors), fast skeletal muscle troponin T, ribosomal protein L3, the integral protein of the peroxisomal membrane 22PMP, the mammalian homolog of geranylgeranyl pyrophosphate synthase, an mRNA related to phosphatidylinositol-glycan-specific phospholipase D, and two unknown mRNAs. The level of overexpression of these mRNAs in skeletal muscle varied from a 500% increase to as little as a 25% increase. Two mRNAs were underexpressed 20-35%, including the f-subunit of mitochondrial ATP synthase and a retrovirus-related DNA. Two proteins with multiple transcripts, skeletal muscle alpha-tropomyosin and one for a repetitive sequence, showed a change in mRNA pattern of expression in the muscle of the ob/ob mouse. Because the primary genetic defect in the ob/ob mouse is known to be in the leptin gene, these data indicate how acquired alterations in gene expression of multiple classes of proteins may play a role in the complex pathogenesis of insulin resistance in obesity and diabetes.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Fleischman, S. Johnsen, D. M. Systrom, M. Hrovat, C. T. Farrar, W. Frontera, K. Fitch, B. J. Thomas, M. Torriani, H. C. F. Cote, et al. Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1666 - E1673. [Abstract] [Full Text] [PDF]

				E. Nisoli, E. Clementi, M. O. Carruba, and S. Moncada Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome? Circ. Res., March 30, 2007; 100(6): 795 - 806. [Abstract] [Full Text] [PDF]

				L. M. Gronning, R. Tingsabadh, K. Hardy, K. T. Dalen, P. S. Jat, L. Gnudi, and P. R. Shepherd Glucose induces increases in levels of the transcriptional repressor Id2 via the hexosamine pathway Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E599 - E606. [Abstract] [Full Text] [PDF]

				M. E. Patti, A. J. Butte, S. Crunkhorn, K. Cusi, R. Berria, S. Kashyap, Y. Miyazaki, I. Kohane, M. Costello, R. Saccone, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1 PNAS, July 8, 2003; 100(14): 8466 - 8471. [Abstract] [Full Text] [PDF]

				S. R. Wesolowski, M. F. Allan, M. K. Nielsen, and D. Pomp Evaluation of hypothalamic gene expression in mice divergently selected for heat loss Physiol Genomics, April 16, 2003; 13(2): 129 - 137. [Abstract] [Full Text] [PDF]

				J.-C. Sanchez, V. Converset, A. Nolan, G. Schmid, S. Wang, M. Heller, M. V. Sennitt, D. F. Hochstrasser, and M. A. Cawthorne Effect of Rosiglitazone on the Differential Expression of Diabetes-associated Proteins in Pancreatic Islets of C57Bl/6 lep/lep Mice Mol. Cell. Proteomics, July 1, 2002; 1(7): 509 - 516. [Abstract] [Full Text] [PDF]

				P. M. Larsen, S.J. Fey, M.R. Larsen, A. Nawrocki, H.U. Andersen, H. Kähler, C. Heilmann, M.C. Voss, P. Roepstorff, F. Pociot, et al. Proteome Analysis of Interleukin-1{beta}-Induced Changes in Protein Expression in Rat Islets of Langerhans Diabetes, May 1, 2001; 50(5): 1056 - 1063. [Abstract] [Full Text]

				M. F. ALLAN, M. K. NIELSEN, and D. POMP Gene expression in hypothalamus and brown adipose tissue of mice divergently selected for heat loss Physiol Genomics, September 8, 2000; 3(3): 149 - 156. [Abstract] [Full Text] [PDF]

				M. Renz, E. Tomlinson, B. Hultgren, N. Levin, Q. Gu, R. A. Shimkets, D. A. Lewin, and T. A. Stewart Quantitative Expression Analysis of Genes Regulated by Both Obesity and Leptin Reveals a Regulatory Loop between Leptin and Pituitary-derived ACTH J. Biol. Chem., March 31, 2000; 275(14): 10429 - 10436. [Abstract] [Full Text] [PDF]

				D. Vicent, E. Maratos-Flier, and C. R. Kahn The Branch Point Enzyme of the Mevalonate Pathway for Protein Prenylation Is Overexpressed in the ob/ob Mouse and Induced by Adipogenesis Mol. Cell. Biol., March 15, 2000; 20(6): 2158 - 2166. [Abstract] [Full Text]

				S. Tartare-Deckert, C. Chavey, M.-N. Monthouel, N. Gautier, and E. Van Obberghen The Matricellular Protein SPARC/Osteonectin as a Newly Identified Factor Up-regulated in Obesity J. Biol. Chem., June 15, 2001; 276(25): 22231 - 22237. [Abstract] [Full Text] [PDF]

				C.-P. Liang and A. R. Tall Transcriptional Profiling Reveals Global Defects in Energy Metabolism, Lipoprotein, and Bile Acid Synthesis and Transport with Reversal by Leptin Treatment in Ob/ob Mouse Liver J. Biol. Chem., December 21, 2001; 276(52): 49066 - 49076. [Abstract] [Full Text] [PDF]