16 January 1998
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-R<sub>L</sub>) with signalling capacity and short isoforms (leptin-R<sub>S</sub>) 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 (E<sub>2</sub>) 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-R<sub>L</sub>. 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-R<sub>L</sub> 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 E<sub>2</sub> administration and increased by OVX. Administration of E<sub>2</sub> reduced leptin-R<sub>L</sub> 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-R<sub>L</sub> mRNA. Fasting also caused a differential regulation of leptin-R mRNAs, with an increase in abundance of leptin-R<sub>L</sub> 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-R<sub>L</sub> transcripts in all brain areas analysed and a decrease in leptin-R gene expression. These results demonstrate a differential regulation of leptin-R<sub>L</sub> and leptin-R<sub>S</sub> 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 E<sub>2</sub> alter the balance between leptin-R<sub>L</sub> and leptin-R<sub>S</sub> and that this could increase tissue sensitivity to leptin.