Document Detail


Programmed hyperphagia due to reduced anorexigenic mechanisms in intrauterine growth-restricted offspring.
MedLine Citation:
PMID:  17644805     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Maternal food restriction during pregnancy results in intrauterine growth-restricted (IUGR) newborns with significantly decreased plasma leptin levels. When nursed by ad libitum-fed controls, IUGR offspring exhibit hyperphagia with adult obesity, marked by increased percentage body fat and plasma leptin, suggesting altered anorexigenic pathways. The authors examined leptin signaling pathways and food intake responses to 2 putative anorexic effectors (leptin and sibutramine, a serotonin reuptake inhibitor) in IUGR offspring. From 10 days to term gestation and through lactation, control pregnant rats received ad libitum food, whereas study rats were 50% food restricted. Following birth, litter size was standardized, and all offspring were nursed by control dams. At 3 weeks of age, offspring were weaned to ad libitum laboratory chow. At ages 1 day and 3 weeks, hypothalamic leptin receptor (Ob-Rb) mRNA and total STAT3 protein expression were determined. In addition, phosphorylated STAT3 was measured in 1-day-old offspring administered peripheral leptin. In prepubescent and adult offspring, anorexic effects of leptin and sibutramine were determined. At 1 day of age, IUGR pups showed increased hypothalamic Ob-Rb mRNA and total STAT3 protein expression though reduced leptin activated phosphorylated STAT3. At 3 weeks of age, IUGR offspring had decreased hypothalamic Ob-Rb mRNA expression, although with continued elevated STAT3 protein levels. The IUGR offspring demonstrated resistance to anorexigenic agents, leptin (6 weeks and 6 months), and sibutramine (8 months), as evidenced by less reduction in food intake and less body weight loss than controls. The IUGR offspring demonstrate suppressed leptin-induced STAT3 phosphorylation and impaired anorexigenic response to 2 factors in the central satiety pathway. This reduced anorexigenic function, together with normal or perhaps enhanced orexigenic function, contributes to the development of programmed obesity in IUGR rat offspring.
Authors:
Mina Desai; Dave Gayle; Guang Han; Michael G Ross
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Reproductive sciences (Thousand Oaks, Calif.)     Volume:  14     ISSN:  1933-7205     ISO Abbreviation:  Reprod Sci     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-07-23     Completed Date:  2007-09-26     Revised Date:  2008-01-21    
Medline Journal Info:
Nlm Unique ID:  101291249     Medline TA:  Reprod Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  329-37     Citation Subset:  IM    
Affiliation:
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David-Geffen School of Medicine, University of California Los Angeles, Torrance, California 90502, USA. mdesai@obgyn.humc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Appetite Depressants / administration & dosage,  pharmacology*
Female
Fetal Growth Retardation / physiopathology*
Hyperphagia / prevention & control*
Hypothalamus / physiopathology
Litter Size
Male
Pregnancy
Rats
Receptors, Cell Surface / genetics
Receptors, Leptin
Reverse Transcriptase Polymerase Chain Reaction
STAT3 Transcription Factor / genetics
Grant Support
ID/Acronym/Agency:
K01 DK 063994/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Appetite Depressants; 0/Receptors, Cell Surface; 0/Receptors, Leptin; 0/STAT3 Transcription Factor; 0/Stat3 protein, mouse

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