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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Hypothalamic AMPK activation blocks lipopolysaccharide inhibition of glucose production in mice liver

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Santos, G. A. [1] ; Moura, R. F. [1] ; Vitorino, D. C. [2] ; Roman, E. A. F. R. [1] ; Torsoni, A. S. [3] ; Velloso, L. A. [1] ; Torsoni, M. A. [3]
Total Authors: 7
[1] Univ Estadual Campinas UNICAMP, Fac Ciencias Aplicadas, Dept Med Interna, Campinas, SP - Brazil
[2] Univ Estadual Campinas UNICAMP, Inst Biol, Dept Fisiol & Biofis, Campinas, SP - Brazil
[3] Univ Estadual Campinas UNICAMP, Fac Ciencias Aplicadas, BR-13484350 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Molecular and Cellular Endocrinology; v. 381, n. 1-2, p. 88-96, DEC 5 2013.
Web of Science Citations: 10

Endotoxic hypoglycaemia has an important role in the survival rates of septic patients. Previous studies have demonstrated that hypothalamic AMP-activated protein kinase (hyp-AMPK) activity is sufficient to modulate glucose homeostasis. However, the role of hyp-AMPK in hypoglycaemia associated with endotoxemia is unknown. The aims of this study were to examine hyp-AMPK dephosphorylation in lipopolysaccharide (LPS)-treated mice and to determine whether pharmacological hyp-AMPK activation could reduce the effects of endotoxemia on blood glucose levels. LPS-treated mice showed reduced food intake, diminished basal glycemia, increased serum TNF-alpha and IL-1 beta levels and increased hypothalamic p-TAK and TLR4/MyD88 association. These effects were accompanied by hyp-AMPK/ACC dephosphorylation. LPS-treated mice also showed diminished liver expression of PEPCK/G6Pase, reduction in p-FOXO1, p-AMPK, p-STAT3 and p-JNK level and glucose production. Pharmacological hyp-AMPK activation blocked the effects of LPS on the hyp-AMPK phosphorylation, liver PEPCK expression and glucose production. Furthermore, the effects of LPS were TLR4-dependent because hyp-AMPK phosphorylation, liver PEPCK expression and fasting glycemia were not affected in TLR4-mutant mice. These results suggest that hyp-AMPK activity may be an important pharmacological target to control glucose homeostasis during endotoxemia. (C) 2013 Elsevier Ireland Ltd. All rights reserved. (AU)

FAPESP's process: 11/17656-0 - Modulation of hypothalamic AMPK and energy homeostasis by LPS: the role of toll like Receptor-4 (TLR-4)
Grantee:Marcio Alberto Torsoni
Support type: Regular Research Grants
FAPESP's process: 09/16775-6 - Toll Like Receptor activation in the hypothalamus rats and the modulation of energy balance: the role of AMPK/ACC and mTOR
Grantee:Daniele Cristina Vitorino
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 10/14034-6 - Modulation of hepatic metabolism of glucose by activation of inflammatory pathway: the role of hypothalamic AMPK and toll like receptor 4 (TLR4)proteins.
Grantee:Gustavo Aparecido dos Santos
Support type: Scholarships in Brazil - Master