Postnatal regulation of hypothalamic neuropeptide expression by leptin: implications for energy balance and body weight regulation.
Leptin is produced mainly by adipose tissue and has been shown to regulate feeding, energy balance and neuroendocrine function. Regulation of energy homeostasis by leptin is thought to be mediated by hypothalamic neuropeptides, at least in adult rodents. The neonatal period is a critical stage of development during which mammals have to optimize caloric intake to support growth and development, as well as maintain body temperature. It is likely that leptin is involved in the transition from preweaning to adult metabolism. To test this hypothesis, we compared the effect of leptin treatment on body weight and adiposity between neonatal and adult mice. We also determined whether well known hypothalamic neuropeptide targets, e.g. neuropeptide Y (NPY), proopiomelanocortin (POMC), agouti-related peptide (AGRP) and cocaine and amphetamine-regulated transcript (CART) were regulated in a pattern consistent with their presumed roles as mediators of leptin action. Once daily intraperitoneal leptin injection for 7 days did not alter body weight, fat content or expression of hypothalamic neuropeptide mRNAs in 10-day-old mice. In contrast, leptin decreased body weight and adiposity, increased CART and suppressed NPY and AGRP mRNA expression in adult mice. These results are consistent with previous studies showing that the timing of leptin's anorectic action develops after weaning. Furthermore, the association between leptin's ability to influence body weight in adult mice but not in neonates, and the regulation of hypothalamic neuropeptide mRNA expression, is consistent with the view that these peptides mediate leptin's effects on energy balance.
Ahima
R S
RS
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, 764 Clinical Research Building, 415 Curie Blvd., 19104, Philadelphia, PA, USA. ahima@mail.med.upenn.edu
Hileman
S M
SM
D054369:Agouti-Related Protein; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005223:Fats / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009478:Neuropeptide Y / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger; D014280:Triglycerides / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D054369:Agouti-Related Protein; D005223:Fats; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D011506:Proteins; D012333:RNA, Messenger; D014280:Triglycerides; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin; D003345:Corticosterone