Document Detail

Jejunal linoleic acid infusions require GLP-1 receptor signaling to inhibit food intake: implications for the effectiveness of Roux-en-Y gastric bypass.
MedLine Citation:
PMID:  21917638     Owner:  NLM     Status:  MEDLINE    
Roux-en-Y gastric bypass surgery results in sustained decreases in food intake and weight loss. A key component is likely the direct delivery of nutrients to the jejunum and resulting changes in levels of gut peptide secretion. Prior work modeling this aspect of the surgery has shown that small-volume, prolonged jejunal infusions of linoleic acid (LA) produce sustained decreases in food intake and weight loss. LA infusions also significantly elevate plasma glucagon-like peptide-1 (GLP-1) levels. To assess a role for the increased circulating GLP-1 in the feeding suppression, we examined the effect of prolonged peripheral minipump administration of the GLP-1 receptor antagonist exendin 9-39 (Ex 9) on the feeding suppression produced by jejunal LA. Using a 2 × 2 design, we infused either saline or LA in the jejunum (7 h/day, 11.4 kcal) for 5 days with a subset of animals from each group receiving either saline or Ex 9 (25 pmol·kg(-1)·min(-1)) continuously via a minipump. The antagonist alone had no effect on food intake. LA reduced daily food intake greatly in excess of the kilocalories infused. Ex 9 completely blocked the feeding suppression produced by the jejunal LA infusion. Ex 9 also attenuated the increase in plasma GLP-1 induced by jejunal LA infusions. These data demonstrate that endogenous GLP-1 receptor signaling is necessary for the reduction in food intake produced by jejunal LA infusions. Whether increased secretion of additional gut peptides is also necessary for such suppressions remains to be determined.
Megan J Dailey; Alexander A Moghadam; Timothy H Moran
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-13
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  301     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-30     Completed Date:  2012-01-23     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1184-90     Citation Subset:  IM    
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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MeSH Terms
Appetite Regulation / drug effects*,  physiology
Down-Regulation / drug effects
Drug Administration Routes
Eating / drug effects
Gastric Bypass*
Infusions, Parenteral
Jejunum* / drug effects
Linoleic Acid / administration & dosage*,  pharmacology
Rats, Sprague-Dawley
Receptors, Glucagon / blood,  metabolism,  physiology*
Signal Transduction / drug effects,  physiology
Treatment Outcome
Grant Support
Reg. No./Substance:
0/Receptors, Glucagon; 0/glucagon-like peptide-1 receptor; 2197-37-7/Linoleic Acid

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