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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 381, n. 1-2, p. 88-96, DEC 5 2013.
• Citações Web of Science: 10

Resumo

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)

• Processo FAPESP: 11/17656-0 - A modulação da AMPK hipotalâmica e da homeostase energética por LPS: a participação de toll like receptor-4 (TLR-4)
• Beneficiário: Marcio Alberto Torsoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/14034-6 - Modulação do metabolismo hepático da glicose pela ativação de vias inflamatórias: a participação das proteínas ampk e toll like receptor (tlr4) hipotalâmicas.
• Beneficiário: Gustavo Aparecido dos Santos
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/16775-6 - ATIVAÇÃO DE "TOLL LIKE RECEPTOR" (TLR) NO HIPOTÁLAMO DE RATOS E A MODULAÇÃO DO BALANÇO ENERGÉTICO: O PAPEL DAS PROTEÍNAS AMPK/ACC E mTOR
• Beneficiário: Daniele Cristina Vitorino
• Modalidade de apoio: Bolsas no Brasil - Doutorado