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 microg/d leptin or 5 microg/d CNTF for four days. Real-time Taqmantrade mark 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.
Ambati
Suresh
S
Department of Animal and Dairy Science, University of Georgia, Athens, GA 30602-2771, USA.
Duan
Jiuhua
J
Duff
Emily
E
Choi
Yang-Ho
YH
Hartzell
Diane L
DL
Della-Fera
Mary Anne
MA
Baile
Clifton A
CA
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis; D013007:Growth Hormone-Releasing Hormone / Q000096:biosynthesis; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D053614:Janus Kinase 2 / Q000096:biosynthesis; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000096:biosynthesis; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D020934:Ciliary Neurotrophic Factor; D007328:Insulin; D020738:Leptin; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone; D011333:Pro-Opiomelanocortin; D013007:Growth Hormone-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D019950:Mitogen-Activated Protein Kinase 1; D000071876:Prostaglandin-E Synthases; C497818:Ptges protein, rat