The contribution of psychosocial stress to the obesity epidemic: an evolutionary approach

Abstract

The Thrifty Gene hypothesis theorizes that during evolution a set of genes has been selected to ensure survival in environments with limited food supply and marked seasonality. Contemporary environments have predictable and unlimited food availability, an attenuated seasonality due to artificial lighting, indoor heating during the winter and air conditioning during the summer, and promote sedentariness and overeating. In this setting the thrifty genes are constantly activated to enhance energy storage. Psychosocial stress and sleep deprivation are other features of modern societies. Stress-induced hypercortisolemia in the setting of unlimited food supply promotes adiposity. Modern man is becoming obese because these ancient mechanisms are efficiently promoting a positive energy balance. We propose that in today's plentifully provisioned societies, where sedentariness and mental stress have become typical traits, chronic activation of the neuroendocrine systems may contribute to the increased prevalence of obesity. We suggest that some of the yet unidentified thrifty genes may be linked to highly conserved energy sensing mechanisms (AMP kinase, mTOR kinase). These hypotheses are testable. Rural societies that are becoming rapidly industrialized and are witnessing a dramatic increase in obesity may provide a historical opportunity to conduct epidemiological studies of the thrifty genotype. In experimental settings, the effects of various forms of psychosocial stress in increasing metabolic efficiency and gene expression can be further tested.

Fig. 1

Genergostat, a single sensor model: This model proposes that thrifty and profligate genes are regulated by a single energy-sensing mechanism which responds differently to states of energy surplus and energy deficit. In a state of positive energy balance (Feast) the increase in energy availability activates (solid lines) an energy-sensing controller (genergostat) which turns on the thrifty genes and deactivates (dotted lines) the profligate ones. These two set of genes also interact with each other (double arrow lines). The system in a state of negative energy balance (Famine) would operate in the opposite direction. “Genergostat” is mediated by two independent, mechanisms activated by states of energy surplus (orex-genergostat) or depletion (anorex-energostat). For example, in a state of negative energy balance (Famine) the decrease in energy availability induces an activation (solid lines) of the anorex-energostat and an inhibition (dotted lines) of the orex-genergostat. The sensor would then activate the catabolic genes (profligate) and inhibit the anabolic (thrifty) ones to exert their catabolic action. A feedback mechanism between these genes can be envisaged to modulate their actions (double arrow lines). The system in a state of positive energy balance (Feast) would operate with a similar but opposite mechanism.

Fig. 2

The second model proposes that thrifty and profligate genes are regulated by two independent mechanisms activated by states of energy surplus (orex-genergostat) or depletion (anorex-energostat). For example, in a state of negative energy balance (Famine) the decrease in energy availability induces an activation (solid lines) of the anorex-energostat and an inhibition (dotted lines) of the orex-genergostat. The sensor would then activate the catabolic genes (profligate) and inhibit the anabolic (thrifty) ones to exert their catabolic action. A feedback mechanism between these genes can be envisaged to modulate their actions (double arrow lines). The system in a state of positive energy balance (Feast) would operate with a similar but opposite mechanism.

Fig. 3

System (entire figure) in energy balance. The areas of the components (physical activity, energy intake) are equal, as no perturbation has been induced on the internal energy (inner circle) of the organism (triangle). The internal energy is table because energy fluxes between body stores (stored energy) and internal energy are constant and energy intake and physical activity match heat generation (heat). The model assumes: 1) Resting energy expenditure is constant; 2) Genome is a regulator of the energy sensing mechanisms and it does not contribute to the energetic fluxes; 3) Energy intake increases internal energy; 4) Physical activity decreases internal energy by increasing heat production. The size of the arrows of the wheels is proportional to the effect and the direction of the arrows indicates the movement of the energy fluxes. Double arrows (↔) indicate stable energy fluxes. Wheels represent the regulatory interactions between the three components (genome, physical activity, energy intake) and the mechanisms controlling the internal energy.

Fig. 4

System (entire circle) in negative energy balance. The contribution of the three components to the system has changed. The genome by assumption remains stable but physical activity and energy intake have increased and decreased, respectively. The effect of these changes is a decrease in internal energy via heat generation and the energy to restore the internal energy comes from energy intake and body stores. The model is based on the same assumptions stated in legend to Fig. 3. The size of the arrows of the wheels is proportional to the effect and the direction of the arrows indicates the movement of the energy fluxes. Wheels represent the regulatory interactions between the three components (genome, physical activity, energy intake) and the mechanisms controlling the internal energy.

Fig. 5

System (outer circle) in positive energy balance. The contribution of the three components to the system has changed. The genome by assumption remains stable but energy intake and physical activity have increased and decreased, respectively. The effect of these changes is an increase in internal energy and the restoration of the internal energy is achieved by storing the energy as tissue and, to some extent, by heat generation. The model is based on the same assumptions stated in legend to Fig. 3. The size of the arrows of the wheels is proportional to the effect and the direction of the arrows indicates the movement of the energy fluxes. Wheels represent the regulatory interactions between the three components (genome, physical activity, energy intake) and the mechanisms controlling the internal energy.

Fig. 6

System in positive energy balance and influence of the stress responses (hypothalamus-pituitary-adrenal (HPA) axis and symphatoadrenal system (SAS)) on the system (entire figure). The increase in energy intake produces a rise in the internal energy (inner circle) which is primarily stored and, to some extent, dissipated as heat to restore the equilibrium of the organism (triangle). The induction of a stress response via the activation of the HPA and SAS produces different effects. The HPA interacts with the genome to modulate energy fluxes but exerts also a stimulating effect (solid line) on energy intake and fat deposition and an inhibiting effect (dotted line) on heat generation via a modulation of the immune system. The SAS has the opposite effects as induce a decrease in appetite and increase in heat generation and fat mobilization. The size of the arrows and wheels is proportional to the effect and the direction of the arrows indicates the movement of the energy fluxes. The model is based on the same assumptions stated in legend to Fig. 3. Double arrows (↔) indicate reciprocal influences. Wheels are non-energetic, regulatory interactions between the three components (genome, physical activity, energy intake) and the mechanisms controlling the internal energy.