Pulmonary delivery of peptide YY for food intake suppression and reduced body weight gain in rats.

Abstract

AIMS:

Peptide YY (PYY) is an endogenous anorectic gut-secreted peptide that has been shown to suppress appetite in animals and humans, when given by injection. This study tested if needle-free pulmonary delivery of PYY enables food intake suppression and reduced body weight gain in rats. The PYY pharmacokinetics and effects on brain neuropeptide levels were also examined.

METHODS:

Rats received single or once-daily 7-day pulmonary administration of saline or PYYs. Food intake and body weight gain were monitored to study the effects of different doses (0.08-0.90 mg/kg) of PYY3-36, PYY1-36 and PYY13-36. Plasma PYY pharmacokinetics were determined via enzyme-linked immunosorbent assay. Changes in orexigenic neuropeptide Y (NPY) and c-Fos protein levels in the hypothalamus arcuate nucleus (ARC) were measured by immunofluorescence microscopy.

RESULTS:

PYY3-36 caused dose-dependent and 4- to 6-h food intake suppression following pulmonary delivery. At 0.80 mg/kg, the effect was significant with 35.1 ± 5.7 and 19.7 ± 4.2% suppression at 4 and 6 h, respectively. Repeated administration for 7 days reduced cumulative body weight gain by 39.4 ± 11.0%. PYY1-36, but not PYY13-36, was equipotent to PYY3-36 in food intake suppression. The plasma PYY concentration reached its peak at 10 min following pulmonary delivery with 12-14% of bioavailability. Increased c-Fos and reduced NPY expressions were observed in the hypothalamus ARC, consistent with the magnitude of food intake suppression by each of the PYYs.

CONCLUSIONS:

Pulmonary delivery of PYY enabled significant 4- to 6-h food intake suppression via 12-14% of lung absorption and hypothalamic ARC interaction, leading to reduced body weight gain in rats.

• Authors: P P Nadkarni, R M Costanzo, M Sakagami
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 13 Issue 5 Pg. 408-17 (May 2011) ISSN: 1463-1326 [Electronic] England
• PMID: 21226821 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Neuropeptide Y
• Peptide Fragments
• Proto-Oncogene Proteins c-fos
• peptide YY (13-36)
• Peptide YY
• peptide YY (3-36)
• peptide YY (1-36)

Topics

• Animals
• Appetite Regulation (drug effects)
• Arcuate Nucleus of Hypothalamus (drug effects, metabolism)
• Dose-Response Relationship, Drug
• Enzyme-Linked Immunosorbent Assay
• Feeding Behavior (drug effects)
• Microscopy, Fluorescence
• Neuropeptide Y (drug effects, metabolism)
• Peptide Fragments (pharmacology)
• Peptide YY (administration & dosage, pharmacokinetics, pharmacology)
• Proto-Oncogene Proteins c-fos (drug effects, metabolism)
• Rats
• Weight Gain (drug effects)