A novel transcript is up-regulated by fasting in the hypothalamus and enhances insulin signalling

J Neuroendocrinol. 2013 Mar;25(3):292-301. doi: 10.1111/j.1365-2826.2012.02378.x.

Abstract

A transcript of unknown function, regulated by fasting and feeding, was identified by microarray analysis. The transcript is up-regulated in the fasting state. An 1168-bp cDNA was cloned from rat hypothalamus and sequenced. This sequence is consistent with adipogenesis down-regulating transcript 3 (AGD3) (also known as human OCC-1) mRNA. A protein sequence identical to AGD3 was determined by mass spectrometry. In the rat brain, AGD3 mRNA is distributed in the arcuate nucleus, ventromedial hypothalamus, amygdaloid nuclei, hippocampus, and somatic cortex. Double in situ hybridisation showed that AGD3 mRNA is co-localised with pro-opiomelanocortin and neuropeptide Y in arcuate nucleus neurones. AGD3 binds with insulin receptor substrate 4 and increases insulin-stimulated phospho-Akt and regulates AMP-activated protein kinase and mammalian target of rapamycin downstream target S6 kinase phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenylate Kinase / metabolism
  • Animals
  • Base Sequence
  • DNA Primers
  • Fasting*
  • Hypothalamus / metabolism
  • Hypothalamus / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Insulin / metabolism*
  • Mass Spectrometry
  • Open Reading Frames
  • RNA, Messenger / genetics*
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism
  • Up-Regulation*

Substances

  • DNA Primers
  • Insulin
  • RNA, Messenger
  • TOR Serine-Threonine Kinases
  • Adenylate Kinase