No abstract

During acute mental stress, the energy supply to the human brain increases by 12%. To determine how the brain controls this demand for energy, 40 healthy young men participated in two sessions (stress induced by the Trier Social Stress Test and non-stress intervention). Subjects were randomly assigned to four different experimental groups according to the energy provided during or after stress intervention (rich buffet, meager salad, dextrose-infusion and lactate-infusion). Blood samples were frequently taken and subjects rated their autonomic and neuroglycopenic symptoms by standard questionnaires. We found that stress increased carbohydrate intake from a rich buffet by 34 g (from 149 ± 13 g in the non-stress session to 183 ± 16 g in the stress session; P < 0.05). While these stress-extra carbohydrates increased blood glucose concentrations, they did not increase serum insulin concentrations. The ability to suppress insulin secretion was found to be linked to the sympatho-adrenal stress-response. Social stress increased concentrations of epinephrine 72% (18.3 ± 1.3 vs. 31.5 ± 5.8 pg/ml; P < 0.05), norepinephrine 148% (242.9 ± 22.9 vs. 601.1 ± 76.2 pg/ml; P < 0.01), ACTH 184% (14.0 ± 1.3 vs. 39.8 ± 7.7 pmol/l; P < 0.05), cortisol 131% (5.4 ± 0.5 vs. 12.4 ± 1.3 μg/dl; P < 0.01) and autonomic symptoms 137% (0.7 ± 0.3 vs. 1.7 ± 0.6; P < 0.05). Exogenous energy supply (regardless of its character, i.e., rich buffet or energy infusions) was shown to counteract a neuroglycopenic state that developed during stress. Exogenous energy did not dampen the sympatho-adrenal stress-responses. We conclude that the brain under stressful conditions demands for energy from the body by using a mechanism, which we refer to as “cerebral insulin suppression” and in so doing it can satisfy its excessive needs.

The brain occupies a special hierarchical position in human energy metabolism. If cerebral homeostasis is threatened, the brain behaves in a “selfish” manner by competing for energy resources with the body. Here we present a logistic approach, which is based on the principles of supply and demand known from economics. In this “cerebral supply chain” model, the brain constitutes the final consumer. In order to illustrate the operating mode of the cerebral supply chain, we take experimental data which allow assessing the supply, demand and need of the brain under conditions of psychosocial stress. The experimental results show that the brain under conditions of psychosocial stress actively demands energy from the body, in order to cover its increased energy needs. The data demonstrate that the stressed brain uses a mechanism referred to as “cerebral insulin suppression” to limit glucose fluxes into peripheral tissue (muscle, fat) and to enhance cerebral glucose supply. Furthermore psychosocial stress elicits a marked increase in eating behavior in the post-stress phase. Subjects ingested more carbohydrates without any preference for sweet ingredients. These experimentally observed changes of cerebral demand, supply and need are integrated into a logistic framework describing the supply chain of the selfish brain.

The hypothalamus-pituitary-adrenal (HPA) system is closely related to stress and the restoration of homeostasis. This system is stimulated in the second half of the night, decreases its activity in the daytime, and reaches the homeostatic level during the late evening. In this paper, we derive and discuss a novel model for the HPA system. It is based on three simple rules that constitute a principle of homeostasis and include only the most substantive physiological elements. In contrast to other models, its main components include, apart from the conventional negative feedback ingredient, a positive feedback loop. To validate the model, we present a parameter estimation procedure that enables one to adapt the model to clinical observations. Using this methodology, we are able to show that the novel model is capable of simulating clinical trials. Furthermore, the stationary state of the system is investigated. We show that, under mild conditions, the system always has a well-defined set-point, which reflects the clinical situation to be modeled. Finally, M. Conrad (B)

Objective: As has been shown recently, obesity is associated with brain volume deficits. We here used an interventional study design to investigate whether the brain shrinks after caloric restriction in obesity. To elucidate mechanisms of neuroprotection we assessed brain-pull competence, i.e. the brain’s ability to properly demand energy from the body. Methods: In 52 normal-weight and 42 obese women (before and after ≈10% weight loss) organ masses of brain, liver and kidneys (magnetic resonance imaging), fat (air displacement plethysmography) and muscle mass (dual-energy X-ray absorptiometry) were assessed. Body metabolism was measured by indirect calorimetry. To investigate how energy is allocated between brain and body, we used reference data obtained in the field of comparative biology. We calculated the distance between each woman and a reference mammal of comparable size in a brain-body plot and named the distance ‘encephalic measure’. To elucidate how the brain protects its mass, we measured fasting insulin, since ‘cerebral insulin suppression’ has been shown to function as a brain-pull mechanism. Results: Brain mass was equal in normal-weight and obese women (1,441.8 ± 14.6 vs. 1,479.2 ± 12.8 g; n.s.) and was unaffected by weight loss (1,483.8 ± 12.7 g; n.s.). In contrast, masses of muscle, fat, liver and kidneys decreased by 3–18% after weight loss (all p < 0.05). The encephalic measure was lower in obese than normal-weight women (5.8 ± 0.1 vs. 7.4 ± 0.1; p < 0.001). Weight loss increased the encephalic measure to 6.3 ± 0.1 (p < 0.001). Insulin concentrations were inversely related to the encephalic measure (r = –0.382; p < 0.001). Conclusion: Brain mass is normal in obese women and is protected during caloric restriction. Our data suggest that neuroprotection during caloric restriction is mediated by a competent brain-pull exerting cerebral insulin suppression.

Feedback control, both negative and positive, is a fundamental feature of biological systems. Some of these systems strive to achieve a state of equilibrium or "homeostasis". The major endocrine systems are regulated by negative feedback, a process believed to maintain hormonal levels within a relatively narrow range. Positive feedback is often thought to have a destabilizing effect. Here, we present a "principle of homeostasis," which makes use of both positive and negative feedback loops. To test the hypothesis that this homeostatic concept is valid for the regulation of cortisol, we assessed experimental data in humans with different conditions (gender, obesity, endocrine disorders, medication) and analyzed these data by a novel computational approach. We showed that all obtained data sets were in agreement with the presented concept of homeostasis in the hypothalamus-pituitary-adrenal axis. According to this concept, a homeostatic system can stabilize itself with the help of a positive feedback loop. The brain mineralocorticoid and glucocorticoid receptors-with their known characteristics-fulfill the key functions in the homeostatic concept: binding cortisol with high and low affinities, acting in opposing manners, and mediating feedback effects on cortisol. This study supports the interaction between positive and negative feedback loops in the hypothalamus-pituitary-adrenal system and in this way sheds new light on the function of dual receptor regulation. Current knowledge suggests that this principle of homeostasis could also apply to other biological systems.

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.

High-calorie comfort food reduces symptoms of neuroglycopenia in Addison patients, suggesting that Addison's disease is associated with a deficit in cerebral energy supply that can partly be alleviated by intake of palatable food. It will be important to investigate whether additional oral glucose supply may be helpful in improving patients' well-being.