Effects of albumin-conjugated PYY on food intake: the respective roles of the circumventricular organs and vagus nerve.
The mechanism and routes through which peptide tyrosine-tyrosine (PYY) exerts its anorectic effects are still largely unknown. In the present study, we investigated the roles of the area postrema (AP), subfornical organ (SFO) and vagus nerve in mediating the anorectic effect of PYY using PYY(3-36) conjugated to human serum albumin (PYY(3-36)-HSA) in rats. PYY(3-36)-HSA is a large molecule that does not penetrate the blood-brain barrier, and thus provides a useful tool to discriminate between the central (brain) and peripheral actions of this peptide. PYY(3-36)-HSA induced significant reductions in food and body weight gain up to 24 h after administration. The anorectic effect of PYY(3-36)-HSA was delayed for 2 h in rats in which both AP and SFO were ablated, while lesion of either of these circumventricular organs in isolation did not influence the feeding responses to PYY(3-36)-HSA. The PYY(3-36)-HSA-induced anorectic effect was also reduced during the 3- to 6-h period following subdiaphragmatic vagotomy. Lesions of AP, SFO and AP/SFO as well as subdiaphragmatic vagotomy blunted PYY(3-36)-HSA-induced expression of c-fos mRNA in specific brain structures including the bed nucleus of stria terminalis, central amygdala, lateral-external parabrachial nucleus and medial nucleus of the solitary tract. In addition, subdiaphragmatic vagotomy inhibited the neuronal activation induced by PYY(3-36)-HSA in AP and SFO. These findings suggest that the anorectic effect and brain neuronal activation induced by PYY(3-36)-HSA are dependent on integrity of AP, SFO and subdiaphragmatic vagus nerve.
Baraboi
Elena-Dana
ED
Merck-Frosst/CIHR Research Chair in Obesity and Institut universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, QC, Canada.
Michel
Chantal
C
Smith
Pauline
P
Thibaudeau
Karen
K
Ferguson
Alastair V
AV
Richard
Denis
D
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology*; D031608:Area Postrema / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000502:physiology; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D009474:Neurons / Q000502:physiology; D010446:Peptide Fragments; D019894:Peptide YY / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*; D013356:Subfornical Organ / Q000187:drug effects / Q000502:physiology*; D014628:Vagotomy / Q000379:methods; D014630:Vagus Nerve / Q000502:physiology
D001067:Appetite Depressants; D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D012709:Serum Albumin; D019894:Peptide YY; C061785:peptide YY (3-36)