Increased ghrelin sensitivity and calorie consumption in subordinate monkeys is affected by short-term astressin B administration

Abstract

Animals chronically exposed to stressors with access to diets high in fat and sugar consume and prefer these diets, a result consistent with the association between stress and comfort food ingestion in humans. As social subordination in rhesus monkeys provides an ethologically relevant translational model of psychosocial stress, we tested the hypothesis that differences in food intake between dominant and subordinate female monkeys are due to corticotropin-releasing hormone-(CRH) induced alteration in sensitivity to ghrelin, a potent orexigenic signal. We assessed food intake of animals given a choice between a low (LCD) and high calorie diet (HCD) in response to 4-day treatment with the CRH receptor antagonist, astressin B, and to an acute treatment of ghrelin. Ghrelin stimulated intake of LCD in subordinates but did not further increase consumption of HCD, whereas ghrelin decreased LCD consumption without affecting HCD intake in dominant females. Astressin B decreased cortisol levels and increased preference for and intake of the HCD in subordinates and decreased calorie intake and HCD preference in dominant animals. These results suggest that increased caloric intake by subordinates may, in part, be explained by a greater sensitivity to postprandial increases in ghrelin and that CRH receptor antagonism leading to a decrease in cortisol has mixed effects on food choice depending on an individual's stress background.

Figure 1

Peripheral cortisol levels (mean ± SEM) for dominant and subordinate animals at the conclusion of each of the two treatment phases. Astressin B decreased peripheral cortisol levels in both dominant and subordinate animals by day four of astressin B treatment (marked by letters).

Figure 2

Mean ± SEM of kcal consumed of LCD (open bar) and HCD (closed bar) following saline or ghrelin IV injection in dominant and subordinate animals over four hours. Ghrelin administration decreased LCD consumption in dominant animals (depicted by *). Conversely, ghrelin increased LCD consumption in subordinate animals (marked by #). There was no main effect of ghrelin, and it did not interact significantly with either status or astressin B administration.

Figure 3

Mean ± SEM of kcal consumed of LCD (open bar) and HCD (closed bar) following saline or astressin B injection in dominant and subordinate animals over four hours. Astressin B administration decreased total intake in dominant animals (depicted by letters). Astressin B increased HCD ingestion in subordinate animals (depicted by *). There was no main effect of astressin B, and it did not interact significantly with either status or ghrelin administration.

Figure 4

Mean ± SEM of the frequency of aggressive (A), submissive (B), and affiliative (C) behaviors per hr following saline (open bar) or ghrelin (closed bar) administration in dominant (D) and subordinate (S) animals during control or astressin B treatments. Dominant animals showed higher rates aggressive behavior in comparison to subordinate animals (A), and subordinate animals showed increased submissive behavior in comparison to dominant animals (B). Dominant animals showed increased affiliative behavior in comparison to subordinate animals, and astressin B increased affiliation only in dominant animals (C). Different letters indicate groups differed significantly (p < 0.05).