Psychosocial stress induces hyperphagia and exacerbates diet-induced insulin resistance and the manifestations of the Metabolic Syndrome.
Stress and hypercaloric food are recognized risk factors for obesity, Metabolic Syndrome (MetS) and Type 2 Diabetes (T2D). Given the complexity of these metabolic processes and the unavailability of animal models, there is poor understanding of their underlying mechanisms. We established a model of chronic psychosocial stress in which subordinate mice are vulnerable to weight gain while dominant mice are resilient. Subordinate mice fed a standard diet showed marked hyperphagia, high leptin, low adiponectin, and dyslipidemia. Despite these molecular signatures of MetS and T2D, subordinate mice fed a standard diet were still euglycemic. We hypothesized that stress predisposes subordinate mice to develop T2D when synergizing with other risk factors. High fat diet aggravated dyslipidemia and the MetS thus causing a pre-diabetes-like state in subordinate mice. Contrary to subordinates, dominant mice were fully protected from stress-induced metabolic disorders when fed both a standard- and a high fat-diet. Dominant mice showed a hyperphagic response that was similar to subordinate but, unlike subordinates, showed a significant increase in VO2, VCO2, and respiratory exchange ratio when compared to control mice. Overall, we demonstrated a robust stress- and social status-dependent effect on the development of MetS and T2D and provided insights on the physiological mechanisms. Our results are reminiscent of the effect of the individual socioeconomic status on human health and provide an animal model to study the underlying molecular mechanisms.
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, USA; Department of Neuroscience, University of Parma, Parma, Italy.
Valentina
V
Sanghez
Maria
M
Razzoli
Stefania
S
Carobbio
Mark
M
Campbell
Jacob
J
McCallum
Cheryl
C
Cero
Graziano
G
Ceresini
Aderville
A
Cabassi
Paolo
P
Govoni
Paolo
P
Franceschini
Valentina
V
de Santis
Allison
A
Gurney
Ivana
I
Ninkovic
Stefano
S
Parmigiani
Paola
P
Palanza
Antonio
A
Vidal-Puig
Alessandro
A
Bartolomucci
D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D002153:Calorimetry, Indirect; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004032:Diet; D059305:Diet, High-Fat; D002149:Energy Intake; D004734:Energy Metabolism; D005951:Glucose Tolerance Test; D006963:Hyperphagia / Q000209:etiology / Q000523:psychology*; D007150:Immunohistochemistry; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000523:psychology*; D051379:Mice; D012307:Risk Factors; D012930:Social Dominance; D012931:Social Environment; D013315:Stress, Psychological / Q000150:complications / Q000523:psychology*
D052242:Adiponectin; D020738:Leptin
Adiponectin; Dominance; Glucose tolerance test; Hyperphagia; Laptin; Social stress; Subiordination; Type 2 diabetes