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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 and time-course analysis of acute stress-induced hyperphagia in C57BL/6J mice. Meal intake was increased over time in subordinate (A), while meal duration (B) was initially increased to later on diminish in correspondence with a meal frequency that remained stable over time (C). Data represent group averages ± SEM. Control: N = 7; subordinate: N = 5. #p = 0.055, *p < 0.05, **p < 0.01.
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Figure 3: Meal-pattern and time-course analysis of acute stress-induced hyperphagia in C57BL/6J mice. Meal intake was increased over time in subordinate (A), while meal duration (B) was initially increased to later on diminish in correspondence with a meal frequency that remained stable over time (C). Data represent group averages ± SEM. Control: N = 7; subordinate: N = 5. #p = 0.055, *p < 0.05, **p < 0.01.

Mentions: Increased hunger- and stress-induced hyperphagia are classically accepted as behavioral markers of BED (10, 31). Hunger-induced hyperphagia was here assessed in both CD1 and C57BL6/J mice in a fasting–refeeding protocol. Subordinate CD1 mice ingested a significantly larger amount of food compared to controls [F(1,23) = 21.88, p < 0.001] (Figure 2A). Similarly, in the 6 h after a single episode of social defeat on the 14th day of the CSS, subordinate mice showed increased food intake [F(1,25) = 5.32, p < 0.05] (Figure 2B). Furthermore, we repeated and extended this observation by using the automated analysis of food intake system. During 6 h immediately following the social defeat, meal intake was significantly increased in subordinate C57BL6/J mice [F(2,8) = 7.12, p < 0.05] (Figure 3A) with a maximal intake occurring after 14 days of stress (p < 0.05). Interestingly, meal duration showed a biphasic effect [F(2,8) = 16.23, p < 0.01] (Figure 3B) being increased on the first day of stress compared to baseline (p < 0.05) and being reduced at day 14 (p < 0.01). Nevertheless, the number of meals exhibited by subordinate mice throughout the stress exposure did not change over time (Figure 3C).


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 and time-course analysis of acute stress-induced hyperphagia in C57BL/6J mice. Meal intake was increased over time in subordinate (A), while meal duration (B) was initially increased to later on diminish in correspondence with a meal frequency that remained stable over time (C). Data represent group averages ± SEM. Control: N = 7; subordinate: N = 5. #p = 0.055, *p < 0.05, **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Meal-pattern and time-course analysis of acute stress-induced hyperphagia in C57BL/6J mice. Meal intake was increased over time in subordinate (A), while meal duration (B) was initially increased to later on diminish in correspondence with a meal frequency that remained stable over time (C). Data represent group averages ± SEM. Control: N = 7; subordinate: N = 5. #p = 0.055, *p < 0.05, **p < 0.01.
Mentions: Increased hunger- and stress-induced hyperphagia are classically accepted as behavioral markers of BED (10, 31). Hunger-induced hyperphagia was here assessed in both CD1 and C57BL6/J mice in a fasting–refeeding protocol. Subordinate CD1 mice ingested a significantly larger amount of food compared to controls [F(1,23) = 21.88, p < 0.001] (Figure 2A). Similarly, in the 6 h after a single episode of social defeat on the 14th day of the CSS, subordinate mice showed increased food intake [F(1,25) = 5.32, p < 0.05] (Figure 2B). Furthermore, we repeated and extended this observation by using the automated analysis of food intake system. During 6 h immediately following the social defeat, meal intake was significantly increased in subordinate C57BL6/J mice [F(2,8) = 7.12, p < 0.05] (Figure 3A) with a maximal intake occurring after 14 days of stress (p < 0.05). Interestingly, meal duration showed a biphasic effect [F(2,8) = 16.23, p < 0.01] (Figure 3B) being increased on the first day of stress compared to baseline (p < 0.05) and being reduced at day 14 (p < 0.01). Nevertheless, the number of meals exhibited by subordinate mice throughout the stress exposure did not change over time (Figure 3C).

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