Study of hypothalamic leptin receptor expression in low-birth-weight piglets and effects of leptin supplementation on neonatal growth and development.
Low birth weight resulting from intrauterine growth retardation (IUGR) is a risk factor for further development of metabolic diseases. The pig appears to reproduce nearly all of the phenotypic pathological consequences of human IUGR and is likely to be more relevant than rodents in studies of neonatal development. In the present work, we characterized the model of low-birth-weight piglets with particular attention to the hypothalamic leptin-sensitive system, and we tested whether postnatal leptin supplementation can reverse the precocious signs of adverse metabolic programming. Our results demonstrated that 1) IUGR piglets present altered postnatal growth and increased adiposity; 2) IUGR piglets exhibit abnormal hypothalamic distribution of leptin receptors that may be linked to further disturbance in food-intake behavior; and 3) postnatal leptin administration can partially reverse the IUGR phenotype by correcting growth rate, body composition, and development of several organs involved in metabolic regulation. We conclude that IUGR may be characterized by altered leptin receptor distribution within the hypothalamic structures involved in metabolic regulation and that leptin supplementation can partially reverse the IUGR phenotype. These results open interesting therapeutic perspectives in physiopathology for the correction of defects observed in IUGR.
Attig
L
L
Université Paris-Sud, Institut National de la Recherche Agronomique, Unité Mixte de Recherche (UMR) 1197, Neurobiologie de l'Olfaction et de la Prise Alimentaire, Jouy-en-Josas. linda.attig@jouy.inra.fr
Djiane
J
J
Gertler
A
A
Rampin
O
O
Larcher
T
T
Boukthir
S
S
Anton
P M
PM
Madec
J Y
JY
Gourdou
I
I
Abdennebi-Najar
L
L
D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D049628:Body Size / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism*; D017403:In Situ Hybridization; D020738:Leptin / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D054411:Receptors, Leptin / Q000235:genetics*; D034421:Sus scrofa / Q000254:growth & development / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D020738:Leptin; D054411:Receptors, Leptin; D014280:Triglycerides