Selfish brain theory
The selfish brain theory describes the ability of the human brain to regulate the energy supply of the organism in such a way that it primarily meets its own needs, which are high compared to other organs . The brain behaves in this respect 'selfishly' - egotistical, engl. selfish . The Selfish Brain Theory provides u. a. a new explanation for the development of obesity (severe form of overweight). The Lübeck obesity specialist and diabetologist Achim Peters worked out the basics of the theory between 1998 and 2004. The interdisciplinary group of scientists "Selfish Brain: Brain Glucose and Metabolic Syndrome" at the University of Lübeck, led by Peters and funded by the German Research Foundation, was able to establish the principles experimentally substantiate the theory. International experts see the research results as groundbreaking for researching the causes of overweight and obesity and the development of innovative intervention options to influence body weight.
The explanatory potential of the selfish brain theory
The concept is based on the special position of the brain in metabolism and body control, because it is characterized by
- its "metabolic compartmentalization",
- high energy consumption,
- a low energy storage capacity,
- its substrate specificity,
- its plasticity,
- the ability to receive information from peripheral organs and to control them in turn.
Research approach of the selfish brain theory
The brain has many functions for the human organism. Most of them are in the cognitive range or concern the control of motor skills. An aspect of brain activity that has not yet been researched is the regulation of energy metabolism. The Selfish Brain Theory shows this in a new light. It says that the brain behaves selfishly in so far as it directs the body's energy supply in such a way that it first allocates energy to itself before the needs of the other organs are satisfied. The brain's own requirements are very high. Although its mass is only 2 percent of body weight, it consumes about two thirds of the carbohydrates it consumes each day . This corresponds to approx. 130 g glucose (grape sugar).
Up until now, science had assumed a parallel energy supply to the brain and muscles and organs. Two control loops played a central role , which are regulated within narrow limits under the control of the hypothalamus , a region of the upper brain stem.
- The "lipostatic theory", set up by Gordon C. Kennedy in 1953, describes the fat control loop. The hypothalamus receives signals from circulating metabolic products or hormones about the volume of adipose tissue and the current metabolic status. Based on these signals, the hypothalamus can adjust food intake so that body fat deposits remain constant, i.e. H. a so-called "lipostasis" is achieved.
- The “glucostatic theory” that Jean Mayer developed in the same year describes the blood sugar control loop. According to this theory, the hypothalamus controls food intake via receptors that determine the glucose content in the blood. In this way, a certain level of glucose concentration is set by means of adapted food intake. Interestingly, Mayer includes the brain in his considerations. For him, food intake serves to secure the energy homeostasis (i.e. self-regulation) of the central nervous system. However, it implicitly assumes that the flow of energy from the body to the brain is a passive process.
On the basis of these theories, international research teams still localize the cause of obesity (obesity) in a disorder in one of the two control loops described above. But there are phenomena in weight regulation that cannot be explained by this. One example is that when you lose weight (e.g. when fasting) almost all organs such as the heart, liver, spleen and kidneys lose weight dramatically (approx. 40 percent), the blood sugar concentration drops, but the brain mass hardly or not at all changes (less than 2 percent on average). Another example shows conflicts between the two explanations: Although obese people release large amounts of the appetite-suppressing hormone leptin , they are plagued by cravings when their blood sugar drops.
The Selfish Brain Theory ties in seamlessly with the tradition of lipostatic and glucostatic theories. What is new is that the Selfish Brain Theory is based for the first time on a further control loop that is superordinate to the blood sugar and fat control loop.
What is meant is a control circuit with which the cerebral hemispheres (the two halves of the brain), the organ of integration of the entire central nervous system, regulate the ATP concentration of their neurons. The cerebral hemispheres thus ensure the primacy of the energy supply to the brain and are therefore seen in the selfish brain theory as the central authority for energy metabolism. When necessary, the cerebral hemispheres cause energy to flow from the body to the brain to maintain energy levels. In contrast to Jean Mayer, the Selfish Brain Theory assumes an active energy on demand process. It is controlled by cerebral ATP sensors, which react sensitively to changes in ATP in the nerve cells of the entire brain.
The Selfish Brain Theory combines the theories of Kennedy and Mayer: It regards the blood sugar and fat control loop as a complex. This regulates the flow of energy from the environment to the body, i. H. the food intake. It is regulated from a hypothalamic core area. Here, too, there are sensitive sensors that register changes in both blood glucose and fat deposits and trigger biochemical processes to maintain a certain body's own balance.
The cerebral hemispheres rely on the subordinate control loop to achieve their goal, the energy homeostasis of the brain. Because they send the signals to their control bodies to procure energy. If these signals are processed differently, for example due to adjustments in the amygdala or hippocampus , the energy supply to the brain is not endangered, but obesity can develop. The cause for this is not to be found in the blood and fat control loop, but in the regulating bodies in the cerebral hemispheres.
The brain supply chain
The Selfish Brain Theory transfers findings from economics on so-called supply chains to the human energy metabolism. The brain is the controller of the supply chain. At the same time, it is also their end user - and not the body through which the supply chains run. The priority of the brain implies that the regulation of the human energy supply is organized not only according to the supply, but also according to the demand principle: Energy is ordered when it is needed ( energy on demand ).
The glucose pathway, from the environment through the body to the brain, bears a marked resemblance to the supply chains that we know from industrial production processes. In logistics, such supply chains have been studied intensively for decades and essential basic principles have been formulated:
- The so-called “push principle” works according to the following rule: The provider offers the material and in this way determines the activity of the production step.
- In contrast to this, the so-called “pull principle” follows the following rule: The material that is required for a production step is only made available when the recipient needs it (“on demand”; “just in time”).
The pull principle has clear economic advantages over the push principle with shorter set-up times and smaller, economically optimized interim storage facilities. Many modern branches of industry have identified and implemented the higher level of competence of pull components. The brain supply chain described here is based on the basic principles of general supply chains. Accordingly, the flows to the brain are regulated by supply and demand. The energy flows to the end user (brain); Disturbances, however, spread in the other direction, i.e. H. Traffic jams form on the path to the end consumer before the supply bottleneck (increase in body weight).
About the figure: If the ATP concentration in the nerve cells of the brain drops even minimally, a cerebral mechanism (brain pull) is set in motion, which increases the body-brain-directed energy flow according to the principle of “energy on demand”. If the energy content in the body (blood, fat tissue) drops, another cerebral mechanism (body pull) is triggered. This causes more energy to be absorbed into the body from the surrounding environment (food intake). When the available supplies in the local area dwindle, another cerebral mechanism (search pull) sets in motion and exploration; H. Foraging in progress.
Energy supply of the brain
The brain meets its energy needs (especially those in the cerebral hemispheres) by first requesting energy from the body. To do this, it activates its stress system (sympathetic nervous system and hypothalamus-pituitary-adrenal system). By activating the stress system, the energy flows in the human organism are redirected to the brain. This function of the stress system to request energy for the brain from the body is called "brain pull" in the supply chain approach. In order for the energy in the body (blood, liver, muscles, fat tissue) to be replenished, the brain then requests energy from the environment: This function of food intake is referred to in the supply chain approach as "body pull". The corresponding signals to the subordinate regulatory systems come from the cerebral hemispheres. The cerebral hemispheres, the phylogenetically youngest part of the brain, are characterized by high plasticity and learning ability in these processes. It can constantly redesign its control processes by processing feedback from the periphery, remembering the results achieved by individual control loops and behaviors and anticipating possible bottlenecks.
The energy procurement of the brain is complicated by three factors:
- First, the brain requests energy when it is needed. It can only store energy in a very limited way. That is why Peters speaks of an "energy-on-demand" system.
- Second, the brain relies primarily on glucose as a substrate for ATP. Lactate and ketones can be used as alternative substrates for brain supply - especially in the case of greater physical or psychological stress or malnutrition.
- Third, the brain is separated from the rest of the body's circulation by the blood-brain barrier . The blood sugar has to be brought there by a special, insulin-independent transporter.
Brain pull mechanisms
The brain pull function is essential for maintaining cerebral energy homeostasis. In the last few years of brain research, several neurobiological mechanisms have been discovered that perform brain pull functions. This enables the brain to request more glucose, lactate or ketones when needed.
Cerebral insulin suppression
The main brain pull mechanism that the brain uses to request more glucose is known as cerebral insulin suppression. The glucose flows are directed either to the brain or to the muscle or fat tissue (figure "cerebral insulin suppression"). The brain measures its energy concentration with the help of energy sensors. When the concentration of energy (ATP) in nerve cells drops, nerve cells in the amygdala , the ventromedial hypothalamus, and the paraventricular nucleus are activated, which in turn stimulate the sympathetic nervous system and the hypothalamic-adrenal system. Both the sympathetic nervous system and the hypothalamus-adrenal cortical system suppress the secretion of insulin by the β-cells in the pancreas. In this way, the glucose transport mediated by the glucose transporter -4 ( GLUT-4 ) into the muscle and fat tissue is reduced. Glucose is thus available for GLUT-1 -mediated glucose uptake in the brain, which is independent of insulin. The brain limits glucose uptake in the peripheral tissues and supplies itself with glucose as needed. Each time the brain pull is activated, the stress hormone cortisol is released into the blood, which from there reacts on the hypothalamus and amygdala. Here, cortisol causes the brain pull to be reduced in the short term, and in the long term, cortisol programs the reactivity of the brain pull system in the higher brain regions. The endocannabinoid system plays an essential role in this long-term programming . This is able to transfer the stress system from a highly reactive mode to a low-reactive mode in the event of permanent stress. The weakening of the reactivity of the stress system equates to habituation of the brain.
Mobilization of lactate or ketones
Two newly discovered neuroendocrine mechanisms serve to procure more lactate or ketones for the brain in stressful life situations, during intense physical exertion or when there is a lack of food. Cerebral Lactate Demand is the name given to the active process in which the brain mobilizes lactate from the skeletal muscles with the help of the activation of the stress system, which reaches the brain via both the blood plasma and the erythrocytes in order to cover the cerebral energy requirements. Ketones (e.g. hydroxybutyrate) are called upon by the brain by activating the stress system to mobilize free fatty acids from the visceral (intra-abdominal) adipose tissue , which reach the liver via the portal vein, where they are converted into ketones, in the large ones Enter the bloodstream and are available to the brain. With chronic stress and sufficient food supply, the permanent stimulation of the sympathetic nerve pathways that innervate this tissue and the permanent influence of cortisol lead to increased cell division and fat accumulation in the visceral fat tissue. This means that the brain has additional energy stores available to cover its energy needs in the event of chronic stress.
Obesity - A 'Supply Chain Jam'
The Selfish Brain Theory is seen as a new approach to understanding obesity . Experimental studies and theoretical considerations of the supply chain of the brain show that the reactivity of the brain pull is the main factor that influences human body weight. In a Norwegian observational study, men whose stress hormones rose sharply in a psychosocial stress test (highly reactive stress system) were protected from weight gain over the next 18 years. In contrast to this, men in this study whose stress hormones increased to a lower value in the stress test (low-reactive stress system) showed a significant increase in weight over the course of the following 18 years. A mathematical analysis also showed that the brain's supply chain has the property that the reactivity of the brain pull is negatively related to the energy content of the body's storage depots. In other words, the higher the reactivity of the brain pull, the lower the body weight and vice versa.
The main reason why the reactivity of the stress system is reduced in humans is psychosocial stress. The reduction in brain-pull reactivity can slowly take place over decades, for example in the case of permanent stress (unemployment, loneliness, poverty, etc.). But it can also suddenly become less reactive due to psychosocial trauma. If there is a low reactive stress system, this leads to the fact that the energy supply for the brain occurs less through brain pull than through body pull (ingestion of food).
If one imagines the energy supply of the human organism as a supply chain (Figure 1), which runs from the outside world with its offers and possibilities of food intake via the body into the brain as end consumer and control organ, then obesity is caused by a jam in the supply chain. This is characterized by a disproportionate accumulation of energy in adipose tissue or in the blood.
A low-reactive stress system is based on an unresponsive sympathetic nervous system (SNS) and an unresponsive hypothalamic-pituitary-adrenal system. The result is that the energy intended for the brain runs predominantly from the blood into the side stores, i.e. H. into adipose tissue and muscles. In order to maintain cerebral energy homeostasis, the brain gives the command to eat more. This is only ended when the brain metabolism is balanced. In the process, an accumulation process escalates - the page memories are filled up more and more. Overweight or obesity arise. In many cases, this is overlaid by the clinical picture of diabetes mellitus from a point in time that depends on the personal disposition of the person concerned. If fat and muscles can no longer absorb energy, it builds up in the blood, which manifests itself as hyperglycaemia (excess sugar).
Working on the Selfish Brain Theory
The basics of the theory
In 1998 Achim Peters designed the basic model of the selfish brain theory and formulated its axioms. In his presentation of the Selfish Brain theory, he is based on around 5000 published data sets from the 'classic' endocrinology-diabetology and modern neurosciences, but argues mathematically with the help of differential equations as well as system theory. This is a novel methodological approach in diabetology; In this respect, the Selfish Brain theory represents a paradigm shift . The regulation of the adenosine triphosphate content , abbreviated to ATP (a kind of energy currency of the organism) in the brain, is of central importance .
Peters assumes a double feedback structure, according to which the ATP content in the nerve cells of the brain is stabilized via measurements from two sensors with different sensitivity and the resulting energy requirements. One, sensitive sensor, registers ATP deficits and triggers a corresponding allocation signal for glucose, which should be satisfied by demands from the body. The other, insensitive sensor is only activated when there is a glucose overhang and sends a signal for setting the glucose allocation. The optimal amount of ATP is determined by comparing the receptor signals.
The stress system, which is closely related to the glucose supply of the brain, also functions according to the same double feedback structure for Peters. If the individual is confronted with a stress-inducing stimulus, they react with an increase in the central nervous information processing and thus with an increased need for glucose in the brain. The hormone cortisol, which is important for regulating the stress reactions, and the hormone adrenaline, which is important for the supply of glucose, are released from the adrenal glands. The amount of cortisol released is determined by comparing a sensitive and an insensitive sensor, analogous to the control of the ATP content. This process ends when the stress system has returned to its resting position.
Peters bases this model on the axioms of the Selfish Brain theory:
- The ATP content in the brain is kept constant within narrow limits, regardless of the state of the body
- The stress system wants to return to its resting state
Integration achievement of the selfish brain theory
The Selfish-Brain-Theory is an integrative concept, because from a methodological point of view it represents the merging of two previously independently pursued research directions. On the one hand, research on peripheral metabolism is integrated, which examines how the energy metabolism works through food intake in the organs of the body . On the other hand, the results of the brain metabolism expert Luc Pellerin from the University of Lausanne were included, who found that the nerve cells of the brain are supplied with energy via the neighboring astrocytes (star cells) when required . This demand-oriented requirement principle of the nerve cells is called energy on demand .
The selfish brain theory recognizes the description of a logistic supply chain in these approaches. The brain not only controls the supply chain, it is also its end user - and not the body through which the supply chain passes. The priority of the brain implies that the regulation of the human energy supply is not organized according to the supply but rather the demand principle: Energy is ordered when it is needed.
The creation of the Selfish Brain research group
After the axioms were formulated in 1998, Achim Peters sought contact with experts in various fields in order to further develop the selfish brain theory. At an early stage he had already compared his considerations with the views of leading international scientists. They include u. a. the Swiss brain metabolism specialist Luc Pellerin, the well-known obesity researcher Denis G. Baskin, the leading international stress researcher Mary Dallman and the renowned neurobiologist Larry W. Swanson. At the University of Lübeck, Achim Peters exchanged the results of his work with the important neuroendocrinologist Horst Lorenz Fehm. One year later, in 1999, there was intensive collaboration with the psychiatrist and psychotherapist Ulrich Schweiger, who is also researching at the University of Lübeck.
In 2004 the interdisciplinary research group “Selfish Brain: Brain Glucose and Metabolic Syndrome” was officially launched with the support of the German Research Foundation (DFG). Achim Peters was appointed head of a specially set up professorship. He succeeded in getting other well-known scientists interested in the project, including Rolf Hilgenfeld , an expert on the SARS virus and developer of the first inhibitor. At this point in time, the research group had 18 scientific sub-project leaders from different areas such as internal medicine, psychiatry, neurobiology, molecular medicine, mathematics, etc. The Advisory Board included Luc Pellerin, Denis Baskin and Mary Dallman. In 2011 the professorship of the head and the core group of the clinical research group "Selfish Brain" at the Medical Faculty of the University of Lübeck were given a budget and consolidated.
Weight intervention according to the Selfish Brain Theory
According to the Selfish-Brain theory, a low-reactive stress system plays a decisive role in the development of obesity. The main reason that the stress system is less responsive is adaptation (habituation) to stress. This can be long-term stress, such as psychosocial stress, or acute-traumatic stress. A low-reactive stress system requires more food intake to maintain cerebral energy homeostasis. Psychosocial stress therefore requires people who are exposed to the stress system to consume more food. Typically, an overload of the stress system is associated with mood swings and depressive symptoms. An adaptation of the stress system - with a reduction in its reactivity - leads to a relief of this system and thus to an improvement in mood. The cost of this brain strategy is that people need to consume more food to feed their brains.
According to the Selfish-Brain-Theory, weight loss through low-calorie diets is unhealthy in the case of chronic stress , since people suffer damage if they do not eat the additional food required by the brain-pull in a low-reactive stress system. Regardless of whether the brain strongly activates the stress system for its supply and thus suppresses insulin secretion (see section on cerebral insulin suppression ) or secures its energy supply through ketone bodies during prolonged fasting (see section on mobilizing ketones ), it must activate the stress system for this . However, a permanently activated stress system causes an overload (“ allostatic load ”), which is associated with damage to the brain and body.
When reducing stress, there are basically two ways of changing social or individual factors.
Reduction of stress loads - social factors
The effectiveness of measures that change social factors was recently demonstrated in a large US social experiment in which around 4,500 people took part. As part of this intervention study, around 1,800 women from districts with a high percentage of poverty were given the opportunity to move to an area with a low percentage of poverty through random selection. The financing for this was guaranteed by vouchers within the framework of state funding. The other part of the women stayed in the parts of the city with a high percentage of poverty. After a 15-year observation period, the women who had moved to better surroundings had a significantly lower prevalence of obesity compared to the women who had stayed in the poorer parts of the city. The study shows that an intervention that enables an individual to move from a highly stressed environment to a calm one has a significant impact on body weight. The reduction of stress factors such as crime, unemployment and tension in families goes hand in hand with a reduction in physical and mental stress and thus with a lower body weight.
Reduction of stress loads - individual factors
To reduce stress, there are also therapeutic strategies that start with the individual. This includes programs such as mindfulness training, emotion regulation and training in need-based action. It has been shown that mindfulness training can lower the concentration of cortisol in the blood and thus contribute to reducing the stress on the organism.
The first therapeutic approaches with emotion regulation and needs-based action to treat people with high body weight exist in the USA, for example. At the University of Southern California, therapist Laurel Mellin has worked with overweight patients for many years. Mellin deliberately refrains from using calorie-reducing diets in her treatment concept and instead offers conversation training. Although Mellin's therapy was not originally based on Selfish Brain research, her therapeutic experience reports are consistent with their findings. Mellin's approach is to regain control of one's own emotional life in order to normalize the brain pull again. To achieve this goal, it is necessary to gain access to your own feelings and desires. Laurel Mellin calls this process “self nurturing”. Specifically, she wants her patients to find a way to deal with their negative feelings (and the resulting underlying conflicts) instead of suppressing them through secondary strategies, such as increased food intake. Mellin's basic assumption is that there are considerable energies in these negative feelings for positive change if you use them. The therapist lists the following negative emotions: anger, sadness, feeling sick, disappointment, loneliness, guilt, insecurity and boredom. Mellin conducted long-term studies on her concept at the University of Southern California. She monitored both adolescent and adult program participants for a period of 1.3 and 2.0 years respectively. As part of a subsequent follow-up observation, she was able to examine 19 study participants over a period of six years. During this period, the subjects underwent various tests with regard to their weight and blood pressure, they completed sports units and were checked for signs of depression. The group met 18 times for two-hour weekly sessions to practice problem-solving and coping strategies. The participants also agreed to practice their skills regularly. In these studies, Laurel Mellin was able to demonstrate the success of her therapy as follows:
- The relative body weight of the 37 adolescent, overweight participants fell by an average of 9.9 percent, while it remained constant for the 29 overweight participants in the control group who did not receive this treatment. (Note: As long as adolescents are still growing, the "relative body weight" is selected using comparison tables to assess the weight curve.)
- The participants in the adult program had lost an average of 7.9 kg after 2 years, without diet and without medication.
- They maintained their new body weight or were able to reduce it further over the next six years.
- The symptoms of depression decreased by 60 percent during therapy, and after six years by up to 80 percent.
- The blood pressure values fell during therapy and did not rise again afterwards.
- 67 percent of the participants who smoked, drank alcohol or took illegal drugs at the start of therapy had severely restricted or stopped using them after one year. After six years it was even 83 percent.
Mellin's therapy can be seen as the first successful program according to the Selfish Brain Theory. The implementation and evaluation of such a structured program is currently pending in German-speaking countries.
Dissenting opinion on lowering blood sugar
The press spokesman for the German Diabetes Society , Andreas Fritsche, explained that in order to control the blood sugar level, it was important to lower blood sugar in order to avoid secondary diseases and that this should also be done with insulin if necessary.
Experimental Evidence - Scope of Theory
In the first DFG funding period from 2004 to 2012, the scientists of the clinical research group "Selfish Brain: Brain Glucose and Metabolic Syndrome" were able to expand the scope of the Selfish Brain Theory in key points through experimental procedures with healthy and sick test subjects. The Lübeck researchers found the following key results in the area of the axioms of theory:
- The brain "selfishly" maintains its own sugar content
- In stressful situations, the brain is always supplied with a greater proportion of energy than the body
- Nerve cells register their ATP content with two sensors of different sensitivity
- The resting state of the stress system is set by two cortisol receptors of different sensitivity
- Cerebral insulin suppression (CIS) has been identified as a major brain pull mechanism
- In people with a high body weight, the energy distribution mechanism in the brain is changed
- In the case of chronic stress, the stress system adapts and becomes less reactive; As a result, the energy flows between the brain and the body are adjusted differently, which requires increased food intake and thus leads to weight gain
The exceptional position of the brain in emaciation (due to fasting, tumor disease) has been experimentally proven for more than 80 years: the body mass decreases, but the mass of the brain hardly or not at all. This axiom of the selfish brain theory was recently supported by studies at the University of Lübeck using state-of-the-art magnetic resonance methods, for example metabolic stress tests.
Some of the results were presented to the specialist audience and a broader public at two international congresses organized by the Selfish Brain research group (2006 and 2010) in Lübeck ( 2nd Selfish Brain Conference ).
- A. Peters: The Selfish Brain: The Causes of Obesity and Type 2 Diabetes from a Neurobiological Perspective . In: Diabetology and Metabolism , 2011, 6, pp. 216-224, abstract .
- A. Peters: The egotistical brain - how the human weight variety is created . In: Ernahrung Umschau 04/2012, pp. 210–218.
- A. Peters: The selfish brain . Ullstein Buchverlag, 2011, ISBN 978-3-550-08854-4 .
- A. Peters: The myth of overweight . C. Bertelsmann Verlag, 2013, ISBN 978-3-570-10149-0 .
- A. Peters, U. Schweiger, L. Pellerin, C. Hubold, KM Oltmanns, M. Conrad, B. Schultes, J. Born, HL Fehm: The selfish brain: competition for energy resources . In: Neuroscience and Biobehavioral Reviews . tape 28 , no. 2 , 2004, ISSN 0149-7634 , p. 143-180 , doi : 10.1016 / j.neubiorev.2004.03.002 , PMID 15172762 .
- selfish-brain.net Partly bilingual website about the work of Selfish-Brain research, with a list of the original papers
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- Expert chat with Professor Achim Peters. German Diabetes Aid, accessed on September 5, 2014 .
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- KM Oltmanns, UH Melchert, HG Scholand-Engler, MC Howitz, B Schultes, U Schweiger, F Hohagen, J Born, A Peters, L Pellerin: Differential energetic response of brain vs. skeletal muscle upon glycemic variations in healthy humans . In: Am J Physiol Regul Integr Comp Physiol , 294, 2008, pp. R12-R16
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