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Build-ups in the supply chain of the brain: on the neuroenergetic cause of obesity and type 2 diabetes mellitus.

Peters A, Langemann D - Front Neuroenergetics (2009)

Bottom Line: In the same way, we demonstrate support of the related hypothesis, which states that under conditions of food deprivation a competent brain-pull mechanism is indispensable for the continuance of the brain s high energy level.In conclusion, we took the viewpoint of integrative physiology and provided evidence for the necessity of brain-pull mechanisms for the benefit of health.Along these lines, our work supports recent molecular findings from the field of neuroenergetics and continues the work on the "Selfish Brain" theory dealing with the maintenance of the cerebral and peripheral energy homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Head of the Clinical Research Group, Brainmetabolism, Neuroenergetics, Obesity and Diabetes, Medical Clinic 1 Lübeck, Germany.

ABSTRACT
Obesity and type 2 diabetes have become the major health problems in many industrialized countries. A few theoretical frameworks have been set up to derive the possible determinative cause of obesity. One concept views that food availability determines food intake, i.e. that obesity is the result of an external energy "push" into the body. Another one views that the energy milieu within the human organism determines food intake, i.e. that obesity is due to an excessive "pull" from inside the organism. Here we present the unconventional concept that a healthy organism is maintained by a "competent brain-pull" which serves systemic homeostasis, and that the underlying cause of obesity is "incompetent brain-pull", i.e. that the brain is unable to properly demand glucose from the body. We describe the energy fluxes from the environment, through the body, towards the brain with a mathematical "supply chain" model and test whether its predictions fit medical and experimental data sets from our and other research groups. In this way, we show data-based support of our hypothesis, which states that under conditions of food abundance incompetent brain-pull will lead to build-ups in the supply chain culminating in obesity and type 2 diabetes. In the same way, we demonstrate support of the related hypothesis, which states that under conditions of food deprivation a competent brain-pull mechanism is indispensable for the continuance of the brain s high energy level. In conclusion, we took the viewpoint of integrative physiology and provided evidence for the necessity of brain-pull mechanisms for the benefit of health. Along these lines, our work supports recent molecular findings from the field of neuroenergetics and continues the work on the "Selfish Brain" theory dealing with the maintenance of the cerebral and peripheral energy homeostasis.

No MeSH data available.


Related in: MedlinePlus

Flow-chart of the brain-supply-chain model. The graphical representation of the mathematical supply-chain model displays the branching of the energy flow between the brain and the side buffer, i.e. the fat/muscle compartment. In the “Discussion” section we will refer to experiments identifying distinct biological mechanisms that can fulfil specific pull-functions in the model. In short, the mechanisms are organized to satisfy the needs of the respective compartment: Firstly, upon the fall of astrocytic ATP concentrations, e.g. due to neuronal excitation, astrocytes use direct brain-pull mechanisms. Secondly, upon a fall of ATP concentrations in the brain, the allocative brain-pull mechanisms are activated (via red dotted arrow). The core of these mechanisms is represented by the ventromedial hypothalamus (VMH) and the sympatho-adrenal system (SNS), which inhibits peripheral glucose uptake in order to enhanced the supply of the brain. Thirdly, upon a fall of the blood glucose concentration, ingestive pull mechanisms in the lateral hypothalamus (LH) are initiated, i.e. food is taken up. Fourthly, upon energy deprivation in the peripheral buffers, the fall of leptin also promotes ingestive behaviour (via green dotted arrow) and prepares peripheral glucose uptake. When blood glucose concentrations rise after food intake, insulin functions as an energy-storage hormone and mediates a push-mechanism, which drives glucose in a glucose-dependent manner from blood to fat/muscle. Fifthly, upon recognition of food deprivation in the immediate vicinity, foraging pull mechanisms are initiated for locomotion and orientation.
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Figure 2: Flow-chart of the brain-supply-chain model. The graphical representation of the mathematical supply-chain model displays the branching of the energy flow between the brain and the side buffer, i.e. the fat/muscle compartment. In the “Discussion” section we will refer to experiments identifying distinct biological mechanisms that can fulfil specific pull-functions in the model. In short, the mechanisms are organized to satisfy the needs of the respective compartment: Firstly, upon the fall of astrocytic ATP concentrations, e.g. due to neuronal excitation, astrocytes use direct brain-pull mechanisms. Secondly, upon a fall of ATP concentrations in the brain, the allocative brain-pull mechanisms are activated (via red dotted arrow). The core of these mechanisms is represented by the ventromedial hypothalamus (VMH) and the sympatho-adrenal system (SNS), which inhibits peripheral glucose uptake in order to enhanced the supply of the brain. Thirdly, upon a fall of the blood glucose concentration, ingestive pull mechanisms in the lateral hypothalamus (LH) are initiated, i.e. food is taken up. Fourthly, upon energy deprivation in the peripheral buffers, the fall of leptin also promotes ingestive behaviour (via green dotted arrow) and prepares peripheral glucose uptake. When blood glucose concentrations rise after food intake, insulin functions as an energy-storage hormone and mediates a push-mechanism, which drives glucose in a glucose-dependent manner from blood to fat/muscle. Fifthly, upon recognition of food deprivation in the immediate vicinity, foraging pull mechanisms are initiated for locomotion and orientation.

Mentions: The energy content in the environment is termed E, the one in the blood B, the one in the brain Y, and the energy content in the fat/muscle compartment F (Figure 2). The energy content in the blood is proportional to the energy concentration in the blood, whereas the size of the fat/muscle compartment may vary. The flux from the environment into the blood is termed jEB, the flux from the blood into the brain jBY and the flux from the blood into the fat jBF. Furthermore, we also assume that the nearby environment is supplied by an abundant remote environment via the flux jin. The consumption of the brain is denoted , and the consumption of the fat/muscle compartment .


Build-ups in the supply chain of the brain: on the neuroenergetic cause of obesity and type 2 diabetes mellitus.

Peters A, Langemann D - Front Neuroenergetics (2009)

Flow-chart of the brain-supply-chain model. The graphical representation of the mathematical supply-chain model displays the branching of the energy flow between the brain and the side buffer, i.e. the fat/muscle compartment. In the “Discussion” section we will refer to experiments identifying distinct biological mechanisms that can fulfil specific pull-functions in the model. In short, the mechanisms are organized to satisfy the needs of the respective compartment: Firstly, upon the fall of astrocytic ATP concentrations, e.g. due to neuronal excitation, astrocytes use direct brain-pull mechanisms. Secondly, upon a fall of ATP concentrations in the brain, the allocative brain-pull mechanisms are activated (via red dotted arrow). The core of these mechanisms is represented by the ventromedial hypothalamus (VMH) and the sympatho-adrenal system (SNS), which inhibits peripheral glucose uptake in order to enhanced the supply of the brain. Thirdly, upon a fall of the blood glucose concentration, ingestive pull mechanisms in the lateral hypothalamus (LH) are initiated, i.e. food is taken up. Fourthly, upon energy deprivation in the peripheral buffers, the fall of leptin also promotes ingestive behaviour (via green dotted arrow) and prepares peripheral glucose uptake. When blood glucose concentrations rise after food intake, insulin functions as an energy-storage hormone and mediates a push-mechanism, which drives glucose in a glucose-dependent manner from blood to fat/muscle. Fifthly, upon recognition of food deprivation in the immediate vicinity, foraging pull mechanisms are initiated for locomotion and orientation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2691548&req=5

Figure 2: Flow-chart of the brain-supply-chain model. The graphical representation of the mathematical supply-chain model displays the branching of the energy flow between the brain and the side buffer, i.e. the fat/muscle compartment. In the “Discussion” section we will refer to experiments identifying distinct biological mechanisms that can fulfil specific pull-functions in the model. In short, the mechanisms are organized to satisfy the needs of the respective compartment: Firstly, upon the fall of astrocytic ATP concentrations, e.g. due to neuronal excitation, astrocytes use direct brain-pull mechanisms. Secondly, upon a fall of ATP concentrations in the brain, the allocative brain-pull mechanisms are activated (via red dotted arrow). The core of these mechanisms is represented by the ventromedial hypothalamus (VMH) and the sympatho-adrenal system (SNS), which inhibits peripheral glucose uptake in order to enhanced the supply of the brain. Thirdly, upon a fall of the blood glucose concentration, ingestive pull mechanisms in the lateral hypothalamus (LH) are initiated, i.e. food is taken up. Fourthly, upon energy deprivation in the peripheral buffers, the fall of leptin also promotes ingestive behaviour (via green dotted arrow) and prepares peripheral glucose uptake. When blood glucose concentrations rise after food intake, insulin functions as an energy-storage hormone and mediates a push-mechanism, which drives glucose in a glucose-dependent manner from blood to fat/muscle. Fifthly, upon recognition of food deprivation in the immediate vicinity, foraging pull mechanisms are initiated for locomotion and orientation.
Mentions: The energy content in the environment is termed E, the one in the blood B, the one in the brain Y, and the energy content in the fat/muscle compartment F (Figure 2). The energy content in the blood is proportional to the energy concentration in the blood, whereas the size of the fat/muscle compartment may vary. The flux from the environment into the blood is termed jEB, the flux from the blood into the brain jBY and the flux from the blood into the fat jBF. Furthermore, we also assume that the nearby environment is supplied by an abundant remote environment via the flux jin. The consumption of the brain is denoted , and the consumption of the fat/muscle compartment .

Bottom Line: In the same way, we demonstrate support of the related hypothesis, which states that under conditions of food deprivation a competent brain-pull mechanism is indispensable for the continuance of the brain s high energy level.In conclusion, we took the viewpoint of integrative physiology and provided evidence for the necessity of brain-pull mechanisms for the benefit of health.Along these lines, our work supports recent molecular findings from the field of neuroenergetics and continues the work on the "Selfish Brain" theory dealing with the maintenance of the cerebral and peripheral energy homeostasis.

View Article: PubMed Central - PubMed

Affiliation: Head of the Clinical Research Group, Brainmetabolism, Neuroenergetics, Obesity and Diabetes, Medical Clinic 1 Lübeck, Germany.

ABSTRACT
Obesity and type 2 diabetes have become the major health problems in many industrialized countries. A few theoretical frameworks have been set up to derive the possible determinative cause of obesity. One concept views that food availability determines food intake, i.e. that obesity is the result of an external energy "push" into the body. Another one views that the energy milieu within the human organism determines food intake, i.e. that obesity is due to an excessive "pull" from inside the organism. Here we present the unconventional concept that a healthy organism is maintained by a "competent brain-pull" which serves systemic homeostasis, and that the underlying cause of obesity is "incompetent brain-pull", i.e. that the brain is unable to properly demand glucose from the body. We describe the energy fluxes from the environment, through the body, towards the brain with a mathematical "supply chain" model and test whether its predictions fit medical and experimental data sets from our and other research groups. In this way, we show data-based support of our hypothesis, which states that under conditions of food abundance incompetent brain-pull will lead to build-ups in the supply chain culminating in obesity and type 2 diabetes. In the same way, we demonstrate support of the related hypothesis, which states that under conditions of food deprivation a competent brain-pull mechanism is indispensable for the continuance of the brain s high energy level. In conclusion, we took the viewpoint of integrative physiology and provided evidence for the necessity of brain-pull mechanisms for the benefit of health. Along these lines, our work supports recent molecular findings from the field of neuroenergetics and continues the work on the "Selfish Brain" theory dealing with the maintenance of the cerebral and peripheral energy homeostasis.

No MeSH data available.


Related in: MedlinePlus