Limits...
The brain's supply and demand in obesity.

Kubera B, Hubold C, Zug S, Wischnath H, Wilhelm I, Hallschmid M, Entringer S, Langemann D, Peters A - Front Neuroenergetics (2012)

Bottom Line: For that purpose it uses a mechanism referred to as "cerebral insulin suppression" (CIS).First, we found a low reactive stress system in obesity.We conclude that the brain of obese people organizes its need, supply, and demand in a low reactive manner.

View Article: PubMed Central - PubMed

Affiliation: Medical Clinic 1, University of Lübeck Lübeck, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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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.

Mentions: Several molecular and cellular mechanisms have already been discovered, which may fulfill the physiological function of CIS (Figure 1): both the medial amygdalar nucleus and the ventromedial hypothalamus contain glucose-responsive neurons, which control the activity of the SNS and the HPA (Miki et al., 2001; Zhou et al., 2010). The medial amygdalar nucleus sends heavy input to the ventromedial hypothalamus and thereby exerts control over its activity (Petrovich et al., 2001). In the ventromedial hypothalamus, ATP-sensitive potassium (KATP) channels have been shown to monitor intracellular ATP (Spanswick et al., 1997). If the cerebral intracellular ATP concentrations fall, ventromedial hypothalamus neurons depolarize due to GABAergic disinhibition (Chan et al., 2007). Via glutamatergic mechanisms they activate the sympatho-adrenal system (Tong et al., 2007). Specific sympathetic efferences project to pancreatic beta-cells and in so doing inhibit insulin secretion (Ahren, 2000). Ventromedial hypothalamus-controlled sympathetic efferences also project to muscle and fat tissue, where they inhibit insulin-dependent glucose transport via GLUT 4 (Mulder et al., 2005). Catecholamines released at nerve endings adjacent to adipocytes interfere with trafficking of GLUT 4 molecules, i.e., they block the translocation of GLUT 4 from the inside of the cell to its cell membrane. Thus, the ventromedial hypothalamus neurons are capable of limiting the flux of glucose from the blood into the peripheral energy stores (muscle and fat tissue). As a consequence, glucose is now available via insulin-independent GLUT1-transport across the blood-brain barrier (Hasselbalch et al., 1995; Seaquist et al., 2001). In this way, CIS can be interpreted as a brain-pull mechanism that functions to demand energy from the body to cover the increased cerebral need during stress.


The brain's supply and demand in obesity.

Kubera B, Hubold C, Zug S, Wischnath H, Wilhelm I, Hallschmid M, Entringer S, Langemann D, Peters A - Front Neuroenergetics (2012)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3297086&req=5

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.
Mentions: Several molecular and cellular mechanisms have already been discovered, which may fulfill the physiological function of CIS (Figure 1): both the medial amygdalar nucleus and the ventromedial hypothalamus contain glucose-responsive neurons, which control the activity of the SNS and the HPA (Miki et al., 2001; Zhou et al., 2010). The medial amygdalar nucleus sends heavy input to the ventromedial hypothalamus and thereby exerts control over its activity (Petrovich et al., 2001). In the ventromedial hypothalamus, ATP-sensitive potassium (KATP) channels have been shown to monitor intracellular ATP (Spanswick et al., 1997). If the cerebral intracellular ATP concentrations fall, ventromedial hypothalamus neurons depolarize due to GABAergic disinhibition (Chan et al., 2007). Via glutamatergic mechanisms they activate the sympatho-adrenal system (Tong et al., 2007). Specific sympathetic efferences project to pancreatic beta-cells and in so doing inhibit insulin secretion (Ahren, 2000). Ventromedial hypothalamus-controlled sympathetic efferences also project to muscle and fat tissue, where they inhibit insulin-dependent glucose transport via GLUT 4 (Mulder et al., 2005). Catecholamines released at nerve endings adjacent to adipocytes interfere with trafficking of GLUT 4 molecules, i.e., they block the translocation of GLUT 4 from the inside of the cell to its cell membrane. Thus, the ventromedial hypothalamus neurons are capable of limiting the flux of glucose from the blood into the peripheral energy stores (muscle and fat tissue). As a consequence, glucose is now available via insulin-independent GLUT1-transport across the blood-brain barrier (Hasselbalch et al., 1995; Seaquist et al., 2001). In this way, CIS can be interpreted as a brain-pull mechanism that functions to demand energy from the body to cover the increased cerebral need during stress.

Bottom Line: For that purpose it uses a mechanism referred to as "cerebral insulin suppression" (CIS).First, we found a low reactive stress system in obesity.We conclude that the brain of obese people organizes its need, supply, and demand in a low reactive manner.

View Article: PubMed Central - PubMed

Affiliation: Medical Clinic 1, University of Lübeck Lübeck, Germany.

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.

No MeSH data available.


Related in: MedlinePlus