The brain's supply and demand in obesity

Abstract

During psychosocial stress, the brain demands extra energy from the body to satisfy its increased needs. For that purpose it uses a mechanism referred to as "cerebral insulin suppression" (CIS). Specifically, activation of the stress system suppresses insulin secretion from pancreatic beta-cells, and in this way energy-particularly glucose-is allocated to the brain rather than the periphery. It is unknown, however, how the brain of obese humans organizes its supply and demand during psychosocial stress. To answer this question, we examined 20 obese and 20 normal weight men in two sessions (Trier Social Stress Test and non-stress control condition followed by either a rich buffet or a meager salad). Blood samples were continuously taken and subjects rated their vigilance and mood by standard questionnaires. First, we found a low reactive stress system in obesity. While obese subjects showed a marked hormonal response to the psychosocial challenge, the cortisol response to the subsequent meal was absent. Whereas the brains of normal weight subjects demanded for extra energy from the body by using CIS, CIS was not detectable in obese subjects. Our findings suggest that the absence of CIS in obese subjects is due to the absence of their meal-related cortisol peak. Second, normal weight men were high reactive during psychosocial stress in changing their vigilance, thereby increasing their cerebral energy need, whereas obese men were low reactive in this respect. Third, normal weight subjects preferred carbohydrates after stress to supply their brain, while obese men preferred fat and protein instead. We conclude that the brain of obese people organizes its need, supply, and demand in a low reactive manner.

Keywords: brain metabolism; brain-pull; cerebral insulin suppression; experimental human study; obesity; selfish brain theory; stress.

Figure 1

A conceptual diagram that shows key physiological mechanisms, which fulfill the brain-pull function of cerebral insulin suppression (CIS). The flux of glucose is either directed to the brain or to muscle and fat. If neuronal ATP concentrations fall, activation of neurons in the amygdala, in the ventromedial hypothalamus (VMH), and in the paraventricular nucleus (PVN) occurs, which in turn activates the sympathetic nervous system and the hypothalamus pituitary adrenal system (SNS and HPA). Both the SNS and the HPA system suppress insulin release from pancreatic beta cells, thereby decreasing glucose transporter 4 (GLUT-4) mediated glucose uptake into muscle and fat. In this way the brain limits glucose uptake in peripheral tissues and procures itself with glucose on demand. Finally, the CIS-brain-pull system is hierarchically organized and adaptive. The strength of the central glucocorticoid feedback determines whether the CIS-brain-pull system reacts in a high or low reactive manner. ACTH, Adrenocorticotropic hormone; E, epinephrine; NE, norepinephrine.

Figure 2

Hormonal and autonomic symptomatic reactivity during stress intervention and non-stress control condition in obese men (colored symbols) and normal weight men (gray symbols). All subjects were offered a rich buffet at the same time (see arrow). Noteworthy, the meal-related cortisol peak was absent in obese subjects during stress intervention (in contrast to normal weight subjects and the non-stress control conditions). Values are means ± SEM; closed symbols, stress intervention and open symbols, non-stress control condition. For comparison, data of normal weight subjects are taken from [Hitze et al. (2010)].

Figure 3

Glucose and insulin concentrations during stress intervention and the non-stress control condition in obese men (red symbols) and normal weight men (gray symbols). All subjects were offered a rich buffet at the same time (see arrow). While normal weight men displayed suppression of insulin (CIS) under stress conditions (that is blood glucose concentrations increased, but were not accompanied by corresponding increases in serum insulin concentrations), dynamical differences in glucose and insulin concentrations between stress intervention and the non-stress control condition were not observable in obese subjects. Legends as in Figure 2.

Figure 4

Vigilance ratings during stress intervention and non-stress control condition in obese (black symbols) and normal weight men (gray symbols). Social stress elicited hypervigilance in normal weight men, but that was not observable in obesity. Original scale of vigilance ratings ranges from 0 to 9. Legends as in Figure 2.

Figure 5

Neuroglycopenic symptoms during stress intervention and non-stress control condition in obese men (colored symbols) and normal weight men (gray symbols). Social stress induced a neuroglycopenic state in normal weight, but that was not detectable in obesity. Original scale of neuroglycopenic symptoms ranges from 0 to 9. Legends as in Figure 2. ^*P < 0.05, significantly different from non-stress control condition, by dependent t-test.

Figure 6

Post-stress macro-nutrient and energy intake in obese men (colored bars) and normal weight men (gray bars) offered a rich buffet or a meager salad; non-stress control condition (white bars). Normal weight men increased their carbohydrate intake, whereas obese men increased fat and protein intake. Legend as in Figure 2. ^*P < 0.05, significantly different from non-stress control condition, by dependent t-test.

Figure 7

Mood ratings during stress intervention and non-stress control condition in obese men (colored symbols) and normal weight men (gray symbols). Mood recovered with resolving HPA overactivation and neuroglycopenia. Original scale of mood ratings ranges from 0 to 9. Legends as in Figure 2. ^*P < 0.05, significantly different from non-stress control condition, by dependent t-test.