Document Detail

Impaired leptin responsiveness in aged rats.
MedLine Citation:
PMID:  10868965     Owner:  NLM     Status:  MEDLINE    
We previously reported that adiposity and serum leptin levels increase with age in male F-344xBN rats and that when physiological levels of serum leptin are manipulated by fasting, there is a corresponding reciprocal change in hypothalamic neuropeptide Y (NPY) mRNA in young rats, but there are no changes in older rats. These findings suggest that the regulation of hypothalamic NPY mRNA by leptin may be impaired with age. To test this hypothesis, we infused saline or leptin for 7 days into ad libitum-fed rats and compared these with saline-infused rats that were pair-fed the amount of food consumed by the leptin-treated rats. We examined daily food consumption, body weight, whole-body oxygen consumption, serum leptin, and NPY mRNA in the hypothalamus. Food consumption decreased by 50% in the leptin-infused compared with the saline-infused young rats but only decreased by 20% in the aged rats. In the leptin-treated young rats, there was a 24% increase in oxygen consumption compared with the pair-fed rats, but there were no changes in oxygen consumption in the aged rats. Leptin infusion diminished hypothalamic NPY levels by nearly 50% compared with pair-fed young rats, whereas there were no changes in the hypothalamic NPY mRNA levels in senescent rats. In summary, aged rats demonstrate a reduced responsiveness to leptin, including a diminished decrease in food intake and no increase in energy expenditure. These diminished responses to leptin were associated with and may be the result of an impaired suppression of hypothalamic NPY mRNA levels. This leptin resistance may be due to either the elevated obesity and serum leptin with age or due to age itself, or both.
P J Scarpace; M Matheny; R L Moore; N Tümer
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Diabetes     Volume:  49     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-07-13     Completed Date:  2000-07-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  431-5     Citation Subset:  AIM; IM    
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, University of Florida College of Medicine, Gainesville 32608-1197, USA.
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MeSH Terms
Adipose Tissue / drug effects
Aging / physiology*
Body Weight / drug effects
Eating / drug effects
Gene Expression / drug effects
Hypothalamus / drug effects,  physiology
Leptin / pharmacology*
Neuropeptide Y / genetics
Oxygen Consumption / drug effects
Rats, Inbred BN
Rats, Inbred F344
Grant Support
Reg. No./Substance:
0/Leptin; 0/Neuropeptide Y

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