Hypothalamic Inhibition of Acetyl-CoA Carboxylase Stimulates Hepatic Counter-Regulatory Response Independent of AMPK Activation in Rats

Autor(es)

Santos, Gustavo A. ^[1] ; Pereira, Vinicius D. ^[1] ; Roman, Erika A. F. R. ^[1] ; Ignacio-Souza, Leticia ^[1] ; Vitorino, Daniele C. ^[2] ; de Moura, Rodrigo Ferreira ^[1] ; Razolli, Daniela S. ^[1] ; Torsoni, Adriana S. ^[3] ; Velloso, Licio A. ^[1] ; Torsoni, Marcio A. ^[3]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Fac Ciencias Med, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Fac Ciencias Aplicadas, Limeira, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 4 APR 23 2013.
• Citações Web of Science: 8

Resumo

Background: Hypothalamic AMPK acts as a cell energy sensor and can modulate food intake, glucose homeostasis, and fatty acid biosynthesis. Intrahypothalamic fatty acid injection is known to suppress liver glucose production, mainly by activation of hypothalamic ATP-sensitive potassium (K(ATP)) channels. Since all models employed seem to involve malonyl-CoA biosynthesis, we hypothesized that acetyl-CoA carboxylase can modulate the counter-regulatory response independent of nutrient availability. Methodology/Principal Findings: In this study employing immunoblot, real-time PCR, ELISA, and biochemical measurements, we showed that reduction of the hypothalamic expression of acetyl-CoA carboxylase by antisense oligonucleotide after intraventricular injection increased food intake and NPY mRNA, and diminished the expression of CART, CRH, and TRH mRNA. Additionally, as in fasted rats, in antisense oligonucleotide-treated rats, serum glucagon and ketone bodies increased, while the levels of serum insulin and hepatic glycogen diminished. The reduction of hypothalamic acetyl-CoA carboxylase also increased PEPCK expression, AMPK phosphorylation, and glucose production in the liver. Interestingly, these effects were observed without modification of hypothalamic AMPK phosphorylation. Conclusion/Significance: Hypothalamic ACC inhibition can activate hepatic counter-regulatory response independent of hypothalamic AMPK activation. (AU)

• Processo FAPESP: 09/12523-2 - Papel da acetil-CoA carboxilase hipotalâmica na resposta contra-regulatória hepática
• Beneficiário: Vinícius Dias Pereira
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 06/05660-5 - Efeito metabólico de nutrientes e hormônios no hipotálamo: o papel da proteína acetil-CoA carboxilase e canais de potássio
• Beneficiário: Marcio Alberto Torsoni
• Linha de fomento: Auxílio à Pesquisa - Regular