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Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder.

Razzoli M, Sanghez V, Bartolomucci A - Front Nutr (2015)

Bottom Line: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect.There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models.Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food intake.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Biology and Physiology, University of Minnesota.

ABSTRACT

Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge eating disorder (BED) is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress induced hyperphagia associated with the development of obesity. Here we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes.

Methods: Adult male mice were exposed to a model of chronic subordination stress associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol was test the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia.

Results: The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair feeding paradigm.

Conclusion: Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food intake.

No MeSH data available.


Related in: MedlinePlus

Meal-pattern analysis highlighted increased food intake in subordinate C57BL/6J mice (A) that was associated to a faster feeding rate (B) and to a shorter satiety ratio (C) than baseline and/or controls. Data represent group averages ± SEM. Control: N = 7; subordinate: N = 5. #p = 0.055, *p < 0.05, **p < 0.01, ***p < 0.001.
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Figure 1: Meal-pattern analysis highlighted increased food intake in subordinate C57BL/6J mice (A) that was associated to a faster feeding rate (B) and to a shorter satiety ratio (C) than baseline and/or controls. Data represent group averages ± SEM. Control: N = 7; subordinate: N = 5. #p = 0.055, *p < 0.05, **p < 0.01, ***p < 0.001.

Mentions: The CSS model has proven a valuable tool to induce a positive energy balance in male mice of various strains including CD1, C57BL6/J, 129SVEV, and others (19–22, 30). Hyperphagia develops shortly after exposing the mice to subordination stress; it remains sustained throughout the stress exposure and is associated to higher body weight gain compared to controls (21). A detailed analysis of control and subordinate mice eating behavior was conducted through an automatic food monitoring system and a dedicated software generating a meal-pattern analysis. Overall, our analysis revealed a consistent CSS-induced disruption of the meal architecture, which is consistent with a BED. The overall amount of food consumed by subordinate mice was significantly greater than during baseline [F(1,10) = 16.50, p < 0.01] and compared to controls [F(1,10) = 8.445, p < 0.05] (Figure 1A). In line with derangements toward a BED-like syndrome, the eating rate was significantly increased [F(1,10) = 6.13, p < 0.05] (Figure 1B), while the satiety ratio was significantly decreased by CSS [interaction F(1,10) = 8.77, p < 0.05. Figure 1C). Conversely, meal frequency, duration, and size, as well as post-meal interval and total meal time were not different between subordinate and control group (Table 1), suggesting that only specific components of satiation were targeted by stress. The lack of changes in other meal parameters could be a compensatory response or imply that long term control of feeding remained intact.


Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder.

Razzoli M, Sanghez V, Bartolomucci A - Front Nutr (2015)

Meal-pattern analysis highlighted increased food intake in subordinate C57BL/6J mice (A) that was associated to a faster feeding rate (B) and to a shorter satiety ratio (C) than baseline and/or controls. Data represent group averages ± SEM. Control: N = 7; subordinate: N = 5. #p = 0.055, *p < 0.05, **p < 0.01, ***p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300527&req=5

Figure 1: Meal-pattern analysis highlighted increased food intake in subordinate C57BL/6J mice (A) that was associated to a faster feeding rate (B) and to a shorter satiety ratio (C) than baseline and/or controls. Data represent group averages ± SEM. Control: N = 7; subordinate: N = 5. #p = 0.055, *p < 0.05, **p < 0.01, ***p < 0.001.
Mentions: The CSS model has proven a valuable tool to induce a positive energy balance in male mice of various strains including CD1, C57BL6/J, 129SVEV, and others (19–22, 30). Hyperphagia develops shortly after exposing the mice to subordination stress; it remains sustained throughout the stress exposure and is associated to higher body weight gain compared to controls (21). A detailed analysis of control and subordinate mice eating behavior was conducted through an automatic food monitoring system and a dedicated software generating a meal-pattern analysis. Overall, our analysis revealed a consistent CSS-induced disruption of the meal architecture, which is consistent with a BED. The overall amount of food consumed by subordinate mice was significantly greater than during baseline [F(1,10) = 16.50, p < 0.01] and compared to controls [F(1,10) = 8.445, p < 0.05] (Figure 1A). In line with derangements toward a BED-like syndrome, the eating rate was significantly increased [F(1,10) = 6.13, p < 0.05] (Figure 1B), while the satiety ratio was significantly decreased by CSS [interaction F(1,10) = 8.77, p < 0.05. Figure 1C). Conversely, meal frequency, duration, and size, as well as post-meal interval and total meal time were not different between subordinate and control group (Table 1), suggesting that only specific components of satiation were targeted by stress. The lack of changes in other meal parameters could be a compensatory response or imply that long term control of feeding remained intact.

Bottom Line: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect.There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models.Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food intake.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Biology and Physiology, University of Minnesota.

ABSTRACT

Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge eating disorder (BED) is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress induced hyperphagia associated with the development of obesity. Here we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes.

Methods: Adult male mice were exposed to a model of chronic subordination stress associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol was test the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia.

Results: The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair feeding paradigm.

Conclusion: Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food intake.

No MeSH data available.


Related in: MedlinePlus