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Endocrinology ; 155(5): 1700-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24564397

ABSTRACT

Apolipoprotein AIV (Apo AIV) and cholecystokinin (CCK) are secreted in response to fat consumption, and both cause satiation via CCK 1 receptor (CCK-1R)-containing vagal afferent nerves to the nucleus of the solitary tract (NTS), where Apo AIV is also synthesized. Fasted male Long-Evans rats received ip CCK-8 or fourth-ventricular (i4vt) Apo AIV alone or in combination. Food intake and c-Fos proteins (a product of the c-Fos immediate-early gene) were assessed. i4vt Apo AIV and/or ip CCK at effective doses reduced food intake and activated c-Fos proteins in the NTS and hypothalamic arcuate nucleus and paraventricular nucleus. Blockade of the CCK-1R by i4vt lorglumide adjacent to the NTS attenuated the satiating and c-Fos-stimulating effects of CCK and Apo AIV, alone or in combination. Maintenance on a high-fat diet (HFD) for 10 weeks resulted in weight gain and attenuation of both the behavioral and c-Fos responses to a greater extent than occurred in low-fat diet-fed and pair-fed HFD animals. These observations suggest that NTS Apo AIV or/and peripheral CCK requires vagal CCK-1R signaling to elicit satiation and that maintenance on a HFD reduces the satiating capacity of these 2 signals.


Subject(s)
Apolipoproteins A/metabolism , Appetite Regulation , Cholecystokinin/metabolism , Nerve Tissue Proteins/metabolism , Neurons, Afferent/metabolism , Receptor, Cholecystokinin A/metabolism , Solitary Nucleus/metabolism , Animals , Apolipoproteins A/administration & dosage , Apolipoproteins A/genetics , Apolipoproteins A/pharmacology , Appetite Depressants/administration & dosage , Appetite Depressants/pharmacology , Appetite Depressants/therapeutic use , Appetite Regulation/drug effects , Appetite Stimulants/administration & dosage , Appetite Stimulants/pharmacology , Appetitive Behavior/drug effects , Behavior, Animal/drug effects , Cholecystokinin/administration & dosage , Cholecystokinin/analogs & derivatives , Cholecystokinin/antagonists & inhibitors , Diet, High-Fat/adverse effects , Hormone Antagonists/administration & dosage , Hormone Antagonists/pharmacology , Infusions, Intraventricular , Injections, Intraperitoneal , Male , Nerve Tissue Proteins/administration & dosage , Nerve Tissue Proteins/agonists , Nerve Tissue Proteins/antagonists & inhibitors , Neurons, Afferent/drug effects , Obesity/drug therapy , Obesity/etiology , Obesity/metabolism , Rats , Rats, Long-Evans , Receptor, Cholecystokinin A/agonists , Receptor, Cholecystokinin A/antagonists & inhibitors , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology , Sincalide/administration & dosage , Sincalide/analogs & derivatives , Sincalide/pharmacology , Solitary Nucleus/drug effects
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