title: Hypothalamic inhibition of acetyl-CoA carboxylase stimulates hepatic counter-regulatory response independent of AMPK activation in rats.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Hypothalamic ACC inhibition can activate hepatic counter-regulatory response independent of hypothalamic AMPK activation.
authors.affiliation: Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Santos
authors.forename: Vinícius D
authors.initials: VD
authors.lastname: Pereira
authors.forename: Erika A F R
authors.initials: EA
authors.lastname: Roman
authors.forename: Leticia
authors.initials: L
authors.lastname: Ignacio-Souza
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Vitorino
authors.forename: Rodrigo Ferreira
authors.initials: RF
authors.lastname: de Moura
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Razolli
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Torsoni
authors.forename: Licio A
authors.initials: LA
authors.lastname: Velloso
authors.forename: Marcio A
authors.initials: MA
authors.lastname: Torsoni
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D004032:Diet; D005786:Gene Expression Regulation; D005943:Gluconeogenesis / Q000502:physiology; D006728:Hormones / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009841:Oligonucleotides / Q000008:administration & dosage; D010766:Phosphorylation; D051381:Rats
chemical_list: D006728:Hormones; D009841:Oligonucleotides; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase