Differential expression and regulation of leptin receptor isoforms in the rat brain: effects of fasting and oestrogen.
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.
Bennett
P A
PA
Division of Neurophysiology, National Institute for Medical Research, London, UK. pbennet@nimr.mrc.ac.uk
Lindell
K
K
Karlsson
C
C
Robinson
I C
IC
Carlsson
L M
LM
Carlsson
B
B
D000818:Animals; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000187:drug effects; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D015342:DNA Probes; D004967:Estrogens / Q000494:pharmacology*; D005215:Fasting / Q000502:physiology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007536:Isomerism; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D011924:Rats, Zucker; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000096:biosynthesis* / Q000187:drug effects*; D054411:Receptors, Leptin
D002352:Carrier Proteins; D015342:DNA Probes; D004967:Estrogens; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin; D004247:DNA