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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

The effect of brain-pull efficiency on the maintenance of cerebral homeostasis under the condition of food restriction in a “supply chain” simulation study. The model is non-dimensional; time is denoted as t. In model 1 (bold line), there is an efficient brain-pull component, in model 2 (thin line) the brain-pull component is inefficient. For both models, the nutritional availability in the environment is set to be restricted from a certain time point onwards. In model 1, the supply-chain model predicts a fall of the blood glucose concentration and a decrease of the energy content in the fat/muscle compartment. The energy content in the brain is only marginally reduced, i.e. energetic brain homeostasis is maintained. In model 2, however, the model predicts a considerable disturbance of the brain energy homeostasis. Besides, the energy uptake from the environment is smaller in model 1 than in model 2, indicating a more economic utilisation of the food offer.
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Figure 3: The effect of brain-pull efficiency on the maintenance of cerebral homeostasis under the condition of food restriction in a “supply chain” simulation study. The model is non-dimensional; time is denoted as t. In model 1 (bold line), there is an efficient brain-pull component, in model 2 (thin line) the brain-pull component is inefficient. For both models, the nutritional availability in the environment is set to be restricted from a certain time point onwards. In model 1, the supply-chain model predicts a fall of the blood glucose concentration and a decrease of the energy content in the fat/muscle compartment. The energy content in the brain is only marginally reduced, i.e. energetic brain homeostasis is maintained. In model 2, however, the model predicts a considerable disturbance of the brain energy homeostasis. Besides, the energy uptake from the environment is smaller in model 1 than in model 2, indicating a more economic utilisation of the food offer.

Mentions: The fluxes at the interfaces of the model are determined by the following three assumptions. Firstly, the inflow jin is assumed to be proportional to an energy deficit in the near environment, i.e. it acts compensatory with respect to an energy set-point E0, the proportionality factor is called lin. Different cases of food abundance are modelled by different proportionality factors describing different difficulties in food acquisition. That means, that an abundant food offer is modelled by a large factor lin, and small deficits in the energy content of the near environment suffice to result in a large inflow. On the other hand, a small factor lin produces the situation that a larger energy deficit in the environment only organizes the necessary energy inflow. Consequently, the environmental compartment is properly filled in the case of an abundant food offer, and it is emptied with a restricted food offer. Hence, the energy content E shows the wealth of the food offer (cf Figures 3 and 4). Secondly, the cerebral energy consumption is essentially related to the degree of neuronal activity, which depends on the level of neuronal stimulation c1 and the available cerebral energy Y required for that process. Thus, the cerebral consumption is supposed to increase in an affine manner with the cerebral energy content (for biological mechanisms that fulfil the function of controlling neuronal consumption in an energy-dependent manner see Table 1). As observed the energy content in the brain is nearly constant, and we will see that the model reproduces this property although the brain energy content is even not mathematically fixed. Thirdly, the energy consumption of the fat/muscle compartment is differentiated into a constant maintenance j0 and a component proportional to its size. Hence, we findFigure 3


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)

The effect of brain-pull efficiency on the maintenance of cerebral homeostasis under the condition of food restriction in a “supply chain” simulation study. The model is non-dimensional; time is denoted as t. In model 1 (bold line), there is an efficient brain-pull component, in model 2 (thin line) the brain-pull component is inefficient. For both models, the nutritional availability in the environment is set to be restricted from a certain time point onwards. In model 1, the supply-chain model predicts a fall of the blood glucose concentration and a decrease of the energy content in the fat/muscle compartment. The energy content in the brain is only marginally reduced, i.e. energetic brain homeostasis is maintained. In model 2, however, the model predicts a considerable disturbance of the brain energy homeostasis. Besides, the energy uptake from the environment is smaller in model 1 than in model 2, indicating a more economic utilisation of the food offer.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: The effect of brain-pull efficiency on the maintenance of cerebral homeostasis under the condition of food restriction in a “supply chain” simulation study. The model is non-dimensional; time is denoted as t. In model 1 (bold line), there is an efficient brain-pull component, in model 2 (thin line) the brain-pull component is inefficient. For both models, the nutritional availability in the environment is set to be restricted from a certain time point onwards. In model 1, the supply-chain model predicts a fall of the blood glucose concentration and a decrease of the energy content in the fat/muscle compartment. The energy content in the brain is only marginally reduced, i.e. energetic brain homeostasis is maintained. In model 2, however, the model predicts a considerable disturbance of the brain energy homeostasis. Besides, the energy uptake from the environment is smaller in model 1 than in model 2, indicating a more economic utilisation of the food offer.
Mentions: The fluxes at the interfaces of the model are determined by the following three assumptions. Firstly, the inflow jin is assumed to be proportional to an energy deficit in the near environment, i.e. it acts compensatory with respect to an energy set-point E0, the proportionality factor is called lin. Different cases of food abundance are modelled by different proportionality factors describing different difficulties in food acquisition. That means, that an abundant food offer is modelled by a large factor lin, and small deficits in the energy content of the near environment suffice to result in a large inflow. On the other hand, a small factor lin produces the situation that a larger energy deficit in the environment only organizes the necessary energy inflow. Consequently, the environmental compartment is properly filled in the case of an abundant food offer, and it is emptied with a restricted food offer. Hence, the energy content E shows the wealth of the food offer (cf Figures 3 and 4). Secondly, the cerebral energy consumption is essentially related to the degree of neuronal activity, which depends on the level of neuronal stimulation c1 and the available cerebral energy Y required for that process. Thus, the cerebral consumption is supposed to increase in an affine manner with the cerebral energy content (for biological mechanisms that fulfil the function of controlling neuronal consumption in an energy-dependent manner see Table 1). As observed the energy content in the brain is nearly constant, and we will see that the model reproduces this property although the brain energy content is even not mathematically fixed. Thirdly, the energy consumption of the fat/muscle compartment is differentiated into a constant maintenance j0 and a component proportional to its size. Hence, we findFigure 3

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