Hypothalamic inhibition of acetyl-CoA carboxylase stimulates hepatic counter-regulatory response independent of AMPK activation in rats

Author(s)

Vinícius Dias Pereira

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2013-01-17

Examining board members

Marcio Alberto Torsoni; Eduardo Rochete Ropelle; Silvana Bordin

• Advisor: Marcio Alberto Torsoni

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. METHODOLOGY/PRINCIPAL FINDINGS: In this study employing immunoblot, realtime 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 diminished the expression of CART, CRH, and TRH mRNA. Additionally, as in fasted rats antisense oligonucleotide-treated rats, increased serum glucagon and ketone bodies were observed along with diminished levels of serum insulin and hepatic glycogen. The reduction of hypothalamic acetyl-CoA carboxylase also increased PEPCK expression, AMPK phosphorylation, and glucose production. 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)

• FAPESP's process: 09/12523-2 - The role of hypothalamic acetyl-CoA carboxilase in the hepatic counter-regulatory response
• Grantee: Vinícius Dias Pereira
• Support Opportunities: Scholarships in Brazil - Master