Neurosci Biobehav Rev. 2004 Apr;28(2):143-80.  Related Articles, Links 

 
The selfish brain: competition for energy resources.

Peters A, Schweiger U, Pellerin L, Hubold C, Oltmanns KM, Conrad M, Schultes B, Born J, Fehm HL.

Department of Internal Medicine, University of Luebeck, Ratzeburger Allee 160, D-23538 Germany.

The brain occupies a special hierarchical position in the organism. It is separated from the general circulation by the blood-brain barrier, has high energy consumption and a low energy storage capacity, uses only specific substrates, and it can record information from the peripheral organs and control them. Here we present a new paradigm for the regulation of energy supply within the organism. The brain gives priority to regulating its own adenosine triphosphate (ATP) concentration. In that postulate, the peripheral energy supply is only of secondary importance. The brain has two possibilities to ensure its energy supply: allocation or intake of nutrients. The term 'allocation' refers to the allocation of energy resources between the brain and the periphery. Neocortex and the limbic-hypothalamus-pituitary-adrenal (LHPA) system control the allocation and intake. In order to keep the energy concentrations constant, the following mechanisms are available to the brain: (1) high and low-affinity ATP-sensitive potassium channels measure the ATP concentration in neurons of the neocortex and generate a 'glutamate command' signal. This signal affects the brain ATP concentration by locally (via astrocytes) stimulating glucose uptake across the blood-brain barrier and by systemically (via the LHPA system) inhibiting glucose uptake into the muscular and adipose tissue. (2) High-affinity mineralocorticoid and low-affinity glucocorticoid receptors determine the state of balance, i.e. the setpoint, of the LHPA system. This setpoint can permanently and pathologically be displaced by extreme stress situations (chronic metabolic and psychological stress, traumatization, etc.), by starvation, exercise, infectious diseases, hormones, drugs, substances of abuse, or chemicals disrupting the endocrine system. Disorders in the 'energy on demand' process or the LHPA-system can influence the allocation of energy and in so doing alter the body mass of the organism. In summary, the presented model includes a newly discovered 'principle of balance' of how pairs of high and low-affinity receptors can originate setpoints in biological systems. In this 'Selfish Brain Theory', the neocortex and limbic system play a central role in the pathogenesis of diseases such as anorexia nervosa and obesity.

PMID: 15172762 [PubMed - in process]

I also think RAAS is intimantly connected to how prone one is to addictive behavior patters, substances of abuse, risk seeking, sterss disorders, depression and obesity.

so if I am highly prone to addictive behavior, substance abuse, and excessive risk seeking whats this say about me?

so if I am highly prone to addictive behavior, substance abuse, and excessive risk seeking whats this say about me?

That you have a defect in D2 signaling in the PFC, aka the "Reward deficiet disorder". Generally caused by lots of stuff the the common ones are a rare genetic polymorphism in D2 receptors or chronic stress/abuse.

I think RAAS a determines how susceptable one is to this state when under chronic stress. IOW when under chronic stress/abuse/trauma some people develop this disorder others do not. I think RAAS determines this.

It basically determines just how easy it is to mess up the HPA.

SO maybe the increase in stress really set it off in addition to a genetic predisposition?

Are you referring to the renin-aldosterone-angiotensin-system?

ACE = angiotensin converting enzyme?

If so, how does an angiotensin II antagonist fits into all this?

Where do you go from here? Are you looking to fix any defects via supplements or drugs? What is your time-table?

You see jsut about every person falls in to one of two camps. Those that shown PVN overdrive where it jsut goes nutts and burns out (if over weight or dieting), and those that show PVN slowdown where it shuts off. I think RAAS activity determines which group an individual falls in to.

Interestingly enough is that both groups on either end are prone to obesity and that there endocrine profile looks similar. But diagnostic tests show differences. for example both groups show depressed SNS activity. However the burn out group shows decreased SNS because of catacholamine depletion where as the slow down group shows reduced synthesis. They also show differences in the CRH/DEX test that measures HPA sensitivity.

So would those with lower Angiotension II signal tend to have low blood pressure, low sex hormones, mild mannered mood, slow twitch muscle expression etc?

I think RAAS does many things. Specifically I am allmost completely convinced that it is how sex hormones determine fat distrobution.

In general there are clear gender differences that show up at puberty, suggesting that sex hormones play a role in how fat cells develop. And there is much truth to this. It turns out that if you take a fat cell from a man's thigh and a woman's thigh, they are functionally identical and essentially indistinguishable physiologically. Even though the man generally has extremely low levels of estrogen.

The difference, practically, is that men don't generally store fat in their legs and women do (i.e. the fat cells in a man's legs are emptier than in the woman's). As I mentioned before, men who store fat in their lower body have the same problems as women to get rid of it. But most men don't.

The same holds true for visceral or abdominal fat from a woman versus a man. The female's visceral/ab fat is physiologically identical to the man's, although she has very low levels of testosterone. Hence, on average, she won't store much triglyceride in those fat cells.

What this suggests is that fat cells in different areas of the body (which, again, are found in both men and women; the difference is in whether men and women actually store calories there as adults) have certain physiological characteristics that occur irrespective of the hormonal setting. So while the hormonal setting may affect where ingested calories get sent, they aren't really controlling the underlying physiology of the fat cells.

Which is fundamentally why blocking estrogen doesn't fix the lower body fat problem. Lower body fat cells act a certain way whether estrogen is present or not, that's how they are genetically wired to act. The same goes for abdominal fat. Regardless of the person's testosterone levels, they are wired to be a certain way. Now it's time to learn what that wiring is and what makes stubborn fat cells stubborn.

Can anyone else add to this? Guesses as to what Lyle's thinking?