Altered responses to orexigenic (AGRP, MCH) and anorexigenic (alpha-MSH, CART) neuropeptides of paraventricular hypothalamic neurons in early postnatally overfed rats.
Food intake and energy expenditure are regulated by neuropeptides in the hypothalamus. While cocaine- and amphetamine-regulated transcript (CART) peptide and melanocortins such as alpha-melanocyte-stimulating hormone (alpha-MSH) are anorexigenic and increase energy expenditure, the endogenous melanocortin receptor antagonist agouti gene-related protein (AGRP), melanin-concentrating hormone (MCH) and neuropeptide Y (NPY) are orexigenic, anabolic peptides. Alterations in the regulatory balance may promote excessive weight gain. The action of these peptides on paraventricular hypothalamic neurons was studied in brain slices of overweight, adult rats previously subjected to early postnatal overfeeding in small litters of only three pups per mother, compared to 12 pups per dam in control litters. CART, melanocortins and NPY significantly excited paraventricular neurons of controls, whereas neurons of small-litter rats were mainly inhibited. Inhibition was dominant following administration of AGRP, MCH and NPY. The altered responses of paraventricular neurons in adult small-litter rats might reflect a general mechanism of neurochemical plasticity and 'malprogramming' of hypothalamic neuropeptidergic systems acquired during the postnatal critical differentiation period, thus leading to permanently altered function of these regulatory systems of body weight.
Davidowa
Helga
H
Johannes-Mueller-Institute of Physiology, Faculty of Medicine (Charité), Humboldt University Berlin, Tucholskystr. 2, D-10117 Berlin, Germany. helga.davidowa@charite.de
Li
Yuzhen
Y
Plagemann
Andreas
A
D054369:Agouti-Related Protein; D000818:Animals; D000831:Animals, Newborn; D021461:Animals, Outbred Strains; D001067:Appetite Depressants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004594:Electrophysiology; D007028:Hypothalamic Hormones / Q000494:pharmacology*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008098:Litter Size; D008543:Melanins / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009433:Neural Inhibition; D009474:Neurons / Q000187:drug effects; D009765:Obesity / Q000503:physiopathology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000503:physiopathology; D010907:Pituitary Hormones / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000521:alpha-MSH / Q000494:pharmacology*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D054369:Agouti-Related Protein; D001067:Appetite Depressants; D007028:Hypothalamic Hormones; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D009419:Nerve Tissue Proteins; D010907:Pituitary Hormones; D011506:Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000521:alpha-MSH; C019463:melanin-concentrating hormone