Differential expression and regulation of leptin receptor isoforms in the rat brain: effects of fasting and oestrogen

Neuroendocrinology. 1998 Jan;67(1):29-36. doi: 10.1159/000054295.


Leptin affects body weight and reproduction mainly via receptors in the central nervous system. Different isoforms of the leptin receptor (leptin-R) exist, including a long isoform (leptin-RL) with signalling capacity and short isoforms (leptin-RS) with unknown function. The aim of this study was to examine leptin-R gene expression in different regions of the brain under conditions with altered body weight, in the female rat, including ovariectomy (OVX), oestradiol (E2) treatment, fasting and a genetic model of obesity (Zucker fa/fa). Leptin-R gene expression was analysed by in situ hybridization using probes recognizing all receptor isoforms (leptin-R) or specifically leptin-RL. Transcripts recognized by the leptin-R probe were abundant in the choroid plexus (CP), arcuate nucleus (ARC), ventromedial nucleus (VMN), thalamus (TH) and piriform cortex (PC). Leptin-RL transcripts were detected in the ARC, VMN, TH and PC but not in the CP. Although no sex difference was observed, leptin-R gene expression was reduced by E2 administration and increased by OVX. Administration of E2 reduced leptin-RL gene expression in the ARC and VMN but did not alter the expression in the TH or PC. OVX had no effect on the expression of leptin-RL mRNA. Fasting also caused a differential regulation of leptin-R mRNAs, with an increase in abundance of leptin-RL transcripts in the TH despite a decrease in leptin-R in this area. Obese Zucker rats had a similar pattern of expression with an increased expression of leptin-RL transcripts in all brain areas analysed and a decrease in leptin-R gene expression. These results demonstrate a differential regulation of leptin-RL and leptin-RS which could provide a mechanism for regulating access to, and sensitivity of, discrete regions of the brain for circulating leptin. We suggest that fasting and E2 alter the balance between leptin-RL and leptin-RS and that this could increase tissue sensitivity to leptin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / anatomy & histology
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology*
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / drug effects
  • Cloning, Molecular
  • DNA / analysis
  • DNA / biosynthesis
  • DNA Probes
  • Estrogens / pharmacology*
  • Fasting / physiology*
  • Female
  • Image Processing, Computer-Assisted
  • In Situ Hybridization
  • Isomerism
  • Male
  • Polymerase Chain Reaction
  • Rats
  • Rats, Zucker
  • Receptors, Cell Surface*
  • Receptors, Cytokine / biosynthesis*
  • Receptors, Cytokine / drug effects*
  • Receptors, Leptin


  • Carrier Proteins
  • DNA Probes
  • Estrogens
  • Receptors, Cell Surface
  • Receptors, Cytokine
  • Receptors, Leptin
  • DNA