Characterization of the effects of pancreatic polypeptide in the regulation of energy balance.
OBJECTIVE
Pancreatic polypeptide (PP) belongs to a family of peptides including neuropeptide Y and peptide YY. We examined the role of PP in the regulation of body weight as well as the therapeutic potential of PP.


METHODS
We measured food intake, gastric emptying, oxygen consumption, and gene expression of hypothalamic neuropeptides, gastric ghrelin, and adipocytokines in mice after administering PP intraperitoneally. Peptide gene expression was also examined in PP-overexpressing mice. Vagal and sympathetic nerve activities were recorded after intravenous administration in rats. Effects of repeated administrations of PP on energy balance and on glucose and lipid metabolism were examined in both ob/ob obese mice and fatty liver Shionogi (FLS)-ob/ob obese mice.


RESULTS
Peripherally administered PP induced negative energy balance by decreasing food intake and gastric emptying while increasing energy expenditure. The mechanism involved modification of expression of feeding-regulatory peptides (decrease in orexigenic neuropeptide Y, orexin, and ghrelin along with an increase in anorexigenic urocortin) and activity of the vagovagal or vagosympathetic reflex arc. PP reduced leptin in white adipose tissue and corticotropin-releasing factor gene expression. The expression of gastric ghrelin and hypothalamic orexin was decreased in PP-overexpressing mice. Repeated administrations of PP decreased body weight gain and ameliorated insulin resistance and hyperlipidemia in both ob/ob obese mice and FLS-ob/ob obese mice. Liver enzyme abnormalities in FLS-ob/ob obese mice were also ameliorated by PP.


CONCLUSIONS
These observations indicate that PP may influence food intake, energy metabolism, and the expression of hypothalamic peptides and gastric ghrelin.
Asakawa
Akihiro
A
Department of Clinical Molecular Medicine, Kobe University Graduate School of Meidicine, Japan.
Inui
Akio
A
Yuzuriha
Hideki
H
Ueno
Naohiko
N
Katsuura
Goro
G
Fujimiya
Mineko
M
Fujino
Masayuki A
MA
Niijima
Akira
A
Meguid
Michael M
MM
Kasuga
Masato
M
D000818:Animals; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005746:Gastric Emptying / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D054439:Ghrelin; D007031:Hypothalamus / Q000378:metabolism; D007274:Injections, Intraperitoneal; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D000068797:Orexins; D010101:Oxygen Consumption / Q000187:drug effects; D010191:Pancreatic Polypeptide / Q000378:metabolism / Q000494:pharmacology*; D036361:Peptide Hormones / Q000235:genetics; D019894:Peptide YY / Q000235:genetics
D002352:Carrier Proteins; D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D036361:Peptide Hormones; D019894:Peptide YY; D010191:Pancreatic Polypeptide