Metabolic Consequences and Vulnerability to Diet-Induced Obesity in Male Mice under Chronic Social Stress

Alessandro Bartolomucci,Paolo Franceschini,Cheryl Cero,Graziano Ceresini,Giacomo Dell'Omo,Aderville Cabassi,Paolo Govoni,Paola Palanza,Harold Dadomo,Stefano Parmigiani,Daniela Berra,Bernhard Baune

doi:10.1371/journal.pone.0004331

Alessandro Bartolomucci, Paolo Franceschini + Show 10 more

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https://doi.org/10.1371/journal.pone.0004331

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Journal: PloS one	Publication Date: Jan 30, 2009
Citations: 175	License type: CC BY 4.0

Affiliation: University of Parma, Foro Italico University of Rome

Abstract

Social and psychological factors interact with genetic predisposition and dietary habit in determining obesity. However, relatively few pre-clinical studies address the role of psychosocial factors in metabolic disorders. Previous studies from our laboratory demonstrated in male mice: 1) opposite status-dependent effect on body weight gain under chronic psychosocial stress; 2) a reduction in body weight in individually housed (Ind) male mice. In the present study these observations were extended to provide a comprehensive characterization of the metabolic consequences of chronic psychosocial stress and individual housing in adult CD-1 male mice. Results confirmed that in mice fed standard diet, dominant (Dom) and Ind had a negative energy balance while subordinate (Sub) had a positive energy balance. Locomotor activity was depressed in Sub and enhanced in Dom. Hyperphagia emerged for Dom and Sub and hypophagia for Ind. Dom also showed a consistent decrease of visceral fat pads weight as well as increased norepinephrine concentration and smaller adipocytes diameter in the perigonadal fat pad. On the contrary, under high fat diet Sub and, surprisingly, Ind showed higher while Dom showed lower vulnerability to obesity associated with hyperphagia. In conclusion, we demonstrated that social status under chronic stress and individual housing deeply affect mice metabolic functions in different, sometime opposite, directions. Food intake, the hedonic response to palatable food as well as the locomotor activity and the sympathetic activation within the adipose fat pads all represent causal factors explaining the different metabolic alterations observed. Overall this study demonstrates that pre-clinical animal models offer a suitable tool for the investigation of the metabolic consequences of chronic stress exposure and associated psychopathologies.

Highlights

The chronic activation of the stress response has been associated with metabolic disorders and altered energy homeostasis [1,2]
Experimental studies in humans have demonstrated that perturbations of the hypothalamus-pituitary-adrencortical (HPA) axis function relate with abdominal obesity [8] and that stress perception strongly associates with a higher waist-to-hype-ratio and body mass index (BMI) [9,10]
The aims of the present study were: 1) to clarify the metabolic consequences of social stress using two models, i.e. chronic psychosocial stress distinguishing between dominants (Dom) and subordinates (Sub) [26,33], and individual housing (Ind) [34]; 2) to characterize for the first time sympathetic system related parameters within visceral adipose fat pads in animals under chronic stress; 3) to determine morphological changes in the adipose tissue; and 4) to determine if the metabolic consequences of stress-exposure might translate into altered vulnerability to high fat diet (HFD)-induced obesity

Summary

Introduction

The chronic activation of the stress response has been associated with metabolic disorders and altered energy homeostasis [1,2]. Sustained concentrations of GCs as observed under chronic stress can increase the salience of pleasurable or compulsive activities (ingesting sucrose, fat, and drugs, or wheelrunning). Experimental studies in humans have demonstrated that perturbations of the hypothalamus-pituitary-adrencortical (HPA) axis function relate with abdominal obesity [8] and that stress perception strongly associates with a higher waist-to-hype-ratio and body mass index (BMI) [9,10]. In patients depression has been associated with the metabolic syndrome and obesity [1], with pre-existing differences in BMI predicting the direction of changes in energy balance determined by job stress [11]. In a cohort of Finnish twins discordant for adult BMI, the obese co-twins showed the highest index of psychosocial stress perception when compared to the lean co-twins [12]

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