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

被引:117
作者
Bennett, PA
Lindell, K
Karlsson, C
Robinson, ICAF
Carlsson, LMS
Carlsson, B
机构
[1] Natl Inst Med Res, Div Neurophysiol, London NW7 1AA, England
[2] Gothenburg Univ, Sahlgrens Univ Hosp, Res Ctr Endocrinol & Metab, Dept Internal Med, Gothenburg, Sweden
关键词
leptin receptor; fasting; Zucker rats; in situ hybridization; gonadal steroids; arcuate nucleus; ventromedial nucleus; choroid plexus; cortex;
D O I
10.1159/000054295
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-L) with signalling capacity and short isoforms (leptin-R-S) 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-2) 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-L. 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-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 administration and increased by OVX. Administration of E-2 reduced leptin-R-L 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-L mRNA. Fasting also caused a differential regulation of leptin-R mRNAs, with an increase in abundance of leptin-R-L 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-L transcripts in all brain areas analysed and a decrease in leptin-R gene expression. 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 leptin-R-L and leptin-R-S and that this could increase tissue sensitivity to leptin.
引用
收藏
页码:29 / 36
页数:8
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