N-acylphosphatidylethanolamine, a gut- derived circulating factor induced by fat ingestion, inhibits food intake.
N-acylphosphatidylethanolamines (NAPEs) are a relatively abundant group of plasma lipids of unknown physiological significance. Here, we show that NAPEs are secreted into circulation from the small intestine in response to ingested fat and that systemic administration of the most abundant circulating NAPE, at physiologic doses, decreases food intake in rats without causing conditioned taste aversion. Furthermore, (14)C-radiolabeled NAPE enters the brain and is particularly concentrated in the hypothalamus, and intracerebroventricular infusions of nanomolar amounts of NAPE reduce food intake, collectively suggesting that its effects may be mediated through direct interactions with the central nervous system. Finally, chronic NAPE infusion results in a reduction of both food intake and body weight, suggesting that NAPE and long-acting NAPE analogs may be novel therapeutic targets for the treatment of obesity.
Gillum
Matthew P
MP
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Zhang
Dongyan
D
Zhang
Xian-Man
XM
Erion
Derek M
DM
Jamison
Rachel A
RA
Choi
Cheolsoo
C
Dong
Jianying
J
Shanabrough
Marya
M
Duenas
Hillary R
HR
Frederick
David W
DW
Hsiao
Jennifer J
JJ
Horvath
Tamas L
TL
Lo
Chun Min
CM
Tso
Pat
P
Cline
Gary W
GW
Shulman
Gerald I
GI
D000577:Amides; D000818:Animals; D001069:Appetite Regulation; D001835:Body Weight; D004041:Dietary Fats / Q000378:metabolism; D063388:Endocannabinoids; D004983:Ethanolamines; D007031:Hypothalamus / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009043:Motor Activity; D009765:Obesity / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000097:blood / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D053719:Tandem Mass Spectrometry
D000577:Amides; D004041:Dietary Fats; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D010714:Phosphatidylethanolamines; D016760:Proto-Oncogene Proteins c-fos; C005958:palmidrol