Gene expression in arcuate nucleus-median eminence of rats treated with leptin or ciliary neurotrophic factor

Ciliary neurotrophic factor (CNTF) and leptin are cytokine-like hormones and act on their corresponding receptors in the hypothalamic arcuate nucleus (ARC). The present study was designed to assess effects of intracerebroventricular (ICV) injection of leptin and CNTF on gene expression in micropunched hypothalamic arcuate nucleus-median eminence (ARC-ME) complex samples from rats. Male Sprague Dawley rats were implanted with lateral cerebroventricular cannulas for administration of control, 10 mu g/d leptin or 5 mu g/d CNTF for four days. Real-time Taqman RT-PCR was used to quantitatively compare the mRNA levels of selected genes in the ARC-ME complex. Leptin and CNTF increased ARC-ME mRNA levels of signal transducer and activator of transcription 3 (STAT3) by 64.5 and 124.7% (p < 0.01), suppressor of cytokine signaling 3 (SOCS3) by 258.9 and 1063.9% (p < 0.01), cocaine and amphetamine regulated transcript (CART) by 102.7 and 123.1% (p < 0.01), and proopiomelanocortin (POMC2) by 374.1 and 264.9% (p < 0.01), respectively. Leptin increased growth hormone releasing hormone (GHRH) by 309.9% (p < 0.01), while CNTF increased janus kinase 2 (JAK2) mRNA by 31.7% (p < 0.01) and decreased gonadotropin releasing hormone 1 (GNRH1) by 59.7% (p < 0.01), mitogen activated protein kinase 1 (MAPK1) by 19.4% (p < 0.05) and tyrosine hydroxylase (TH) by 74.5% (p < 0.05). Significant reduction in daily food intake and body weights by both the treatments was observed. Also, decrease in weights of fat pads was concomitant with lowered serum insulin and leptin levels. Our findings show that leptin and CNTF engage both convergent and divergent pathways involved in feeding, cellular signaling, inflammation, and other related regulatory systems.