| Large litter rearing enhances leptin sensitivity and protects selectively bred diet-induced obese rats from becoming obese. | |
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MedLine Citation:
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PMID: 20668022 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Because rearing rats in large litters (LLs) protects them from becoming obese, we postulated that LL rearing would protect rats selectively bred to develop diet-induced obesity (DIO) from becoming obese by overcoming their inborn central leptin resistance. Male and female DIO rats were raised in normal litters (NLs; 10 pups/dam) or LLs (16 pups/dam) and assessed for anatomical, biochemical, and functional aspects of leptin sensitivity at various ages when fed low-fat chow or a 31% fat high-energy (HE) diet. LL rearing reduced plasma leptin levels by postnatal day 2 (P2) and body weight gain by P8. At P16, LL DIO neonates had increased arcuate nucleus (ARC) binding of leptin to its extracellular receptors and at P28 an associated increase of their agouti-related peptide and alpha-MSH axonal projections to the paraventricular nucleus. Reduced body weight persisted and was associated with increased ARC leptin receptor binding and sensitivity to the anorectic effects of leptin, reduced adiposity, and enhanced insulin sensitivity in LL DIO rats fed chow until 10 wk of age. The enhanced ARC leptin receptor binding and reduced adiposity of LL DIO rats persisted after an additional 5 wk on the HE diet. Female LL DIO rats had similar reductions in weight gain on both chow and HE diet vs. normal litter DIO rats. We postulate that LL rearing enhances DIO leptin sensitivity by lowering plasma leptin levels and thereby increasing leptin receptor availability and that this both enhances the ARC-paraventricular nucleus pathway development and protects them from becoming obese. |
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Authors:
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Christa M Patterson; Sebastien G Bouret; Sunny Park; Boman G Irani; Ambrose A Dunn-Meynell; Barry E Levin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-07-28 |
Journal Detail:
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Title: Endocrinology Volume: 151 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-25 Completed Date: 2010-10-04 Revised Date: 2011-09-13 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 4270-9 Citation Subset: AIM; IM |
Affiliation:
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Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adiposity
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physiology Agouti-Related Protein / metabolism Animals Animals, Newborn Arcuate Nucleus / metabolism Body Weight / physiology Breeding Diet* Eating / physiology Female Gestational Age Immunohistochemistry Lactation / physiology Leptin / blood*, metabolism Litter Size / physiology* Male Obesity / blood, etiology, physiopathology* Paraventricular Hypothalamic Nucleus / metabolism Protein Binding Rats Receptors, Leptin / metabolism Time Factors Weaning Weight Gain / physiology alpha-MSH / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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F31-NS-050903/NS/NINDS NIH HHS; NIDDK R01-30066//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/AGRP protein, rat; 0/Agouti-Related Protein; 0/Leptin; 0/Receptors, Leptin; 581-05-5/alpha-MSH |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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