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Am J Physiol Endocrinol Metab (July 5, 2005). doi:10.1152/ajpendo.00220.2005
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Submitted on May 13, 2005
Accepted on July 1, 2005

Fat digestion is required for the suppression of ghrelin and stimulation of peptide YY and pancreatic polypeptide secretion by intraduodenal lipid

Christine Feinle-Bisset1*, Michael Patterson1, Mohammad A Ghatei1, Stephen R Bloom1, and Michael Horowitz1

1 Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia

* To whom correspondence should be addressed. E-mail: christine.feinle{at}adelaide.edu.au.

Stimulation of cholecystokinin and glucagon-like peptide-1 secretion by fat is mediated by the products of fat digestion. Ghrelin, peptide YY (PYY) and pancreatic polypeptide (PP) appear to play an important role in appetite regulation and their release is modulated by food ingestion, including fat. It is unknown whether fat digestion is a prerequisite for their suppression (ghrelin) or release (PYY, PP). Moreover, it is not known whether small intestinal exposure to fat is sufficient to suppress ghrelin secretion. Our study aimed to resolve these issues. 16 healthy, young males received, on two separate occasions, 120 min intraduodenal infusions of a long-chain triglyceride emulsion (2.8 kcal/min), (i) without (condition FAT) or (ii) with (FAT-THL) 120 mg of tetrahydrolipstatin (THL, lipase inhibitor), followed by a standard buffet-style meal. Blood samples for ghrelin, PYY and PP were taken throughout. FAT infusion was associated with a marked, and progressive, suppression of plasma ghrelin from t = 60 min (P < 0.001) and stimulation of PYY from t = 30 min (P < 0.01). FAT infusion also stimulated plasma PP (P ≤ 0.01), and the release was immediate. FAT-THL completely abolished the FAT-induced changes in ghrelin, PYY and PP. In response to the meal, plasma ghrelin was further suppressed and PYY and PP stimulated during both FAT and FAT-THL infusions. In conclusion, in healthy humans: (i) the presence of fat in the small intestine suppresses ghrelin secretion and (ii) fat-induced suppression of ghrelin and stimulation of PYY and PP is dependent on fat digestion.




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