| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 23, 2004
Accepted on June 30, 2005
Departments of Internal Medicine and Physiology and Biophysics, State University of Campinas, 13084-970, Campinas - SP; Department of Physiology and Biophysics, University of São Paulo, 05508-900, São Paulo - SP, Brazil
* To whom correspondence should be addressed. E-mail: lavelloso{at}fcm.unicamp.br.
Obesity has reached epidemic proportions in several regions of the world. General changes in lifestyle, including consumption of fat-rich food, are among the most important factors leading to an unprecedented increase in the prevalence of this disease. Weight gain results from an imbalance between caloric intake and energy expenditure. Both of these parameters are under the tight control of specialized neurons of the hypothalamus that respond to peripheral anorexigenic and adipostatic signals carried by leptin and insulin. Here we show, by macroarray analysis, that high-fat feeding (hyperlipidic diet - HL) induces the expression of several pro-inflammatory cytokines and inflammatory responsive proteins in hypothalamus. This phenomenon is accompanied by increased activation of JNK and NF
B. In addition, HL feeding leads to impaired functional and molecular activation of the insulin-signaling pathway, which is paralleled by increased serine phosphorylation of the insulin receptor and IRS-2. Intracerebroventricular (icv) treatment of HL rats with a specific inhibitor of JNK (SP600125) restores insulin signaling and leads to a reduced caloric intake and weight loss. We conclude that HL feeding induces a local pro-inflammatory status in the hypothalamus, which results in impaired anorexigenic insulin signaling.
This article has been cited by other articles:
 |
|
 |
|
  M. Srinivasan, P. Mitrani, G. Sadhanandan, C. Dodds, S. Shbeir-ElDika, S. Thamotharan, H. Ghanim, P. Dandona, S. U Devaskar, and M. S Patel A high-carbohydrate diet in the immediate postnatal life of rats induces adaptations predisposing to adult-onset obesity J. Endocrinol., June 1, 2008; 197(3): 565 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Boullu-Ciocca, V. Achard, V. Tassistro, A. Dutour, and M. Grino Postnatal Programming of Glucocorticoid Metabolism in Rats Modulates High-Fat Diet-Induced Regulation of Visceral Adipose Tissue Glucocorticoid Exposure and Sensitivity and Adiponectin and Proinflammatory Adipokines Gene Expression in Adulthood Diabetes, March 1, 2008; 57(3): 669 - 677. [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]
|
|
|
|
|
|
R. Barbuio, M. Milanski, M. B Bertolo, M. J Saad, and L. A Velloso Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet J. Endocrinol., September 1, 2007; 194(3): 539 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Morton Hypothalamic leptin regulation of energy homeostasis and glucose metabolism J. Physiol., September 1, 2007; 583(2): 437 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Daubert, M.-Y. Chung, and V. L. Brooks Insulin resistance and impaired baroreflex gain during pregnancy Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2188 - R2195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. De Souza, E. P. Araujo, L. F. Stoppiglia, J. R. Pauli, E. Ropelle, S. A. Rocco, R. M. Marin, K. G. Franchini, J. B. Carvalheira, M. J. Saad, et al. Inhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects on both insulin secretion and action FASEB J, April 1, 2007; 21(4): 1153 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pitombo, E. P Araujo, C. T De Souza, J. C Pareja, B. Geloneze, and L. A Velloso Amelioration of diet-induced diabetes mellitus by removal of visceral fat J. Endocrinol., December 1, 2006; 191(3): 699 - 706. [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]
|
|
|
|
 |
|
 C. Ueno, K. Fukatsu, W. Kang, Y. Maeshima, H. Nagayoshi, J. Omata, H. Saito, H. Hiraide, and H. Mochizuki Lack of Enteral Nutrition Delays Nuclear Factor Kappa B Activation in Peritoneal Exudative Cells in a Murine Glycogen-Induced Peritonitis Model JPEN J Parenter Enteral Nutr, May 1, 2006; 30(3): 179 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Kohn, B. Wallace, F. Schwartz, and K. McCall Is Type 2 Diabetes an Autoimmune-Inflammatory Disorder of the Innate Immune System? Endocrinology, October 1, 2005; 146(10): 4189 - 4191. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
