DIFFERENTIAL EXPRESSION AND REGULATION OF LEPTIN RECEPTOR ISOFORMS INTHE RAT-BRAIN - EFFECTS OF FASTING AND ESTROGEN

Leptin affects body weight and reproduction mainly via receptors in th e central nervous system. Different isoforms of the leptin receptor (l eptin-R) exist, including a long isoform (leptin-R-L) with signalling capacity and short isoforms (leptin-R-S) with unknown function. The ai m of this study was to examine leptin-R gene expression in different r egions of the brain under conditions with altered body weight, in the female rat, including ovariectomy (OVX), oestradiol (E-2) treatment, f asting and a genetic model of obesity (Zucker fa/fa). Leptin-R gene ex pression was analysed by in situ hybridization using probes recognizin g all receptor isoforms (leptin-R) or specifically leptin-R-L. Transcr ipts recognized by the leptin-R probe were abundant in the choroid ple xus (CP), arcuate nucleus (ARC), ventromedial nucleus (VMN), thalamus (TH) and piriform cortex (PC). Leptin-R-L 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-2 administrat ion and increased by OVX. Administration of E-2 reduced leptin-R-L gen e expression in the ARC and VMN but did not alter the expression in th e TH or PC. OVX had no effect on the expression of leptin-R-L mRNA. Fa sting also caused a differential regulation of leptin-R mRNAs, with an increase in abundance of leptin-R-L transcripts in the TH despite a d ecrease in leptin-R in this area. Obese Zucker rats had a similar patt ern of expression with an increased expression of leptin-R-L transcrip ts in all brain areas analysed and a decrease in leptin-R gene express ion. These results demonstrate a differential regulation of leptin-R-L and leptin-R-S 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-2 alter the balance between lept in-R-L and leptin-R-S and that this could increase tissue sensitivity to leptin.