This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prada, P. O. Articles by Saad, M. J. A. Search for Related Content PubMed PubMed Citation Articles by Prada, P. O. Articles by Saad, M. J. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB GLUCOSE

Western Diet Modulates Insulin Signaling, c-Jun N-Terminal Kinase Activity, and Insulin Receptor Substrate-1^ser307 Phosphorylation in a Tissue-Specific Fashion

Departamento de Clínica Médica da Universidade Estadual de Campinas, Campinas, São Paulo 13083-970, Brazil

Address all correspondence and requests for reprints to: M. J. A. Saad, Departamento de Clínica Médica, FCM-UNICAMP, Cidade Universitária, Campinas, São Paulo 13083-970, Brazil. E-mail: msaad{at}fcm.unicamp.br.

The mechanisms by which diet-induced obesity is associated with insulin resistance are not well established, and no study has until now integrated, in a temporal manner, functional insulin action data with insulin signaling in key insulin-sensitive tissues, including the hypothalamus. In this study, we evaluated the regulation of insulin sensitivity by hyperinsulinemic-euglycemic clamp procedures and insulin signaling, c-jun N-terminal kinase (JNK) activation and insulin receptor substrate (IRS)-1^ser307 phosphorylation in liver, muscle, adipose tissue, and hypothalamus, by immunoprecipitation and immunoblotting, in rats fed on a Western diet (WD) or control diet for 10 or 30 d. WD increased visceral adiposity, serum triacylglycerol, and insulin levels and reduced whole-body glucose use. After 10 d of WD (WD10) there was a decrease in IRS-1/phosphatidylinositol 3-kinase/protein kinase B pathway in hypothalamus and muscle, associated with an attenuation of the anorexigenic effect of insulin in the former and reduced glucose transport in the latter. In WD10, there was an increased glucose transport in adipose tissue in parallel to increased insulin signaling in this tissue. After 30 d of WD, insulin was less effective in suppressing hepatic glucose production, and this was associated with a decrease in insulin signaling in the liver. JNK activity and IRS-1^ser307 phosphorylation were higher in insulin-resistant tissues. In summary, the insulin resistance induced by WD is tissue specific and installs first in hypothalamus and muscle and later in liver, accompanied by activation of JNK and IRS-1^ser307 phosphorylation. The impairment of the insulin signaling in these tissues, but not in adipose tissue, may lead to increased adiposity and insulin resistance in the WD rats.

This article has been cited by other articles:

				M. P. Feldkaemper, I. Neacsu, and F. Schaeffel Insulin Acts as a Powerful Stimulator of Axial Myopia in Chicks Invest. Ophthalmol. Vis. Sci., January 1, 2009; 50(1): 13 - 23. [Abstract] [Full Text] [PDF]

				P. K. Picardi, V. C. Calegari, P. de Oliveira Prada, J. Contin Moraes, E. Araujo, M. C. C. Gomes Marcondes, M. Ueno, J. B. C. Carvalheira, L. A. Velloso, and M. J. Abdalla Saad Reduction of Hypothalamic Protein Tyrosine Phosphatase Improves Insulin and Leptin Resistance in Diet-Induced Obese Rats Endocrinology, August 1, 2008; 149(8): 3870 - 3880. [Abstract] [Full Text] [PDF]

				A. L Rodrigues, E. P G De Souza, S. V Da Silva, D. S B Rodrigues, A. B Nascimento, C. Barja-Fidalgo, and M. S De Freitas Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition J. Endocrinol., December 1, 2007; 195(3): 485 - 494. [Abstract] [Full Text] [PDF]

				E. P. Araujo, C. T. De Souza, M. Ueno, D. E. Cintra, M. B. Bertolo, J. B. Carvalheira, M. J. Saad, and L. A. Velloso Infliximab Restores Glucose Homeostasis in an Animal Model of Diet-Induced Obesity and Diabetes Endocrinology, December 1, 2007; 148(12): 5991 - 5997. [Abstract] [Full Text] [PDF]

				L. Didier, B. Yerby, R. Deacon, and J. Gao Diet-induced modulation of mitochondrial activity in rat muscle Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1169 - E1177. [Abstract] [Full Text] [PDF]

				H. G. Zecchin, F. B.M. Priviero, C. T. Souza, K. G. Zecchin, P. O. Prada, J. B.C. Carvalheira, L. A. Velloso, E. Antunes, and M. J.A. Saad Defective Insulin and Acetylcholine Induction of Endothelial Cell-Nitric Oxide Synthase Through Insulin Receptor Substrate/Akt Signaling Pathway in Aorta of Obese Rats Diabetes, April 1, 2007; 56(4): 1014 - 1024. [Abstract] [Full Text] [PDF]

				E. R. Ropelle, J. R. Pauli, P. O. Prada, C. T. de Souza, P. K. Picardi, M. C. Faria, D. E. Cintra, M. F. d. A. Fernandes, M. B. Flores, L. A. Velloso, et al. Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation J. Physiol., December 15, 2006; 577(3): 997 - 1007. [Abstract] [Full Text] [PDF]

				M. B.S. Flores, M. F. A. Fernandes, E. R. Ropelle, M. C. Faria, M. Ueno, L. A. Velloso, M. J.A. Saad, and J. B.C. Carvalheira Exercise Improves Insulin and Leptin Sensitivity in Hypothalamus of Wistar Rats Diabetes, September 1, 2006; 55(9): 2554 - 2561. [Abstract] [Full Text] [PDF]

				K. Strle, S. R. Broussard, R. H. McCusker, W.-H. Shen, J. M. LeCleir, R. W. Johnson, G. G. Freund, R. Dantzer, and K. W. Kelley C-Jun N-Terminal Kinase Mediates Tumor Necrosis Factor-{alpha} Suppression of Differentiation in Myoblasts Endocrinology, September 1, 2006; 147(9): 4363 - 4373. [Abstract] [Full Text] [PDF]

				M. H M Lima, L. C Souza, L. C Caperuto, E. Bevilacqua, A. L Gasparetti, R. Zanuto, M. J A Saad, and C. R O Carvalho Up-regulation of the phosphatidylinositol 3-kinase/protein kinase B pathway in the ovary of rats by chronic treatment with hCG and insulin. J. Endocrinol., August 1, 2006; 190(2): 451 - 459. [Abstract] [Full Text] [PDF]

				E. Prodi and S. Obici Minireview: The Brain as a Molecular Target for Diabetic Therapy Endocrinology, June 1, 2006; 147(6): 2664 - 2669. [Abstract] [Full Text] [PDF]

				I. Talukdar, W. Szeszel-Fedorowicz, and L. M. Salati Arachidonic Acid Inhibits the Insulin Induction of Glucose-6-phosphate Dehydrogenase via p38 MAP Kinase J. Biol. Chem., December 9, 2005; 280(49): 40660 - 40667. [Abstract] [Full Text] [PDF]