Hyperleptinemia in A(y)/a mice upregulates arcuate cocaine- and amphetamine-regulated transcript expression.
The effects of leptin on cocaine- and amphetamine-regulated transcript (CART) and agouti-related protein (AGRP) expression in the hypothalamic arcuate nucleus of obese A(y)/a mice were investigated. CART mRNA expression was upregulated by 41% and AGRP mRNA downregulated by 78% in hyperleptinemic A(y)/a mice relative to levels in lean a/a mice. The mRNA expression of these neuropeptides in either young nonobese A(y)/a mice or rats treated with SHU-9119, a synthetic melanocortin-4 receptor (MC4R) antagonist, did not differ significantly from that in the corresponding controls. After a 72-h fast, which decreased the concentration of serum leptin, CART and AGRP mRNA expression decreased and increased, respectively, in A(y)/a mice. The expression levels of these neuropeptides in leptin-deficient A(y)/a ob/ob double mutants were comparable to those in a/a ob/ob mice. Leptin thus modulates both CART and AGRP mRNA expression in obese A(y)/a mice, whereas leptin signals are blocked at the MCR4R level. Taken together, the present findings indicate that differential expression of these neuropeptides in A(y)/a and ob/ob mice results in dissimilar progression toward obesity.
Tsuruta
Yoshio
Y
Department of Internal Medicine I, School of Medicine, Oita Medical University, Oita 879-5593, Japan.
Yoshimatsu
Hironobu
H
Hidaka
Shuji
S
Kondou
Seiya
S
Okamoto
Kenjiro
K
Sakata
Toshiie
T
D054369:Agouti-Related Protein; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001835:Body Weight; D005786:Gene Expression Regulation / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000097:blood*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics*; D018377:Neurotransmitter Agents / Q000235:genetics; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012335:RNA, Ribosomal / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D011506:Proteins; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C103272:SHU 9119; D009074:Melanocyte-Stimulating Hormones