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Homeostatic and Non-Homeostatic Pathways Involved in the Control of Food Intake and Energy Balance.

Berthoud H. Homeostatic and non-homeostatic pathways involved in the control of food intake and energy balance. Obesity (Silver Spring). 2006 Aug;14 Suppl 5:197S-200S.

A neural network sensitive to leptin and other energy status signals stretching from the hypothalamus to the caudal medulla has been identified as the homeostatic control system for the regulation of food intake and energy balance. While this system is remarkably powerful in defending the lower limits of adiposity, it is weak in curbing appetite in a world of plenty. Another extensive neural system that processes appetitive and rewarding aspects of food intake is mainly interacting with the external world. This non-homeostatic system is constantly attacked by sophisticated signals from the environment, ultimately resulting in increased energy intake in many genetically predisposed individuals. Recent findings suggest a role for accumbens-hypothalamic pathways in the interaction between non-homeostatic and homeostatic factors that control food intake. Identification of the neural pathways that mediate this dominance of cortico-limbic processes over the homeostatic regulatory circuits in the hypothalamus and brainstem will be important for the development of behavioral strategies and pharmacological therapies in the fight against obesity.

My comments: this isn’t the kind of uber-technical paper I usually like to deal with in the research review because I don’t figure most readers care so much about the detailed neurobiological stuff; they want application. But this will tie in heavily with a future article series examining the physiological and psychological issues that relate to dieting and fat loss and gives some important background to them.

The basic gist of this paper is that the body has two different systems that ‘regulate’ food intake (and by extension, body weight). Those are homeostatic and non-homeostatic systems.

Some definitions are in order:
Regulation simply refers to the idea that a certain system, via feeding back onto itself, will maintain itself within a fairly narrow range. The best example of a regulated system I can give you is that of your thermostat or maybe cruise control. Your thermostat takes input (temperature), runs that through the processor (what you want the temperature to be) and sets up an output (turns on the heat or the air conditioning). So, depending on where you set the thermostat, the temperature in your house stays fairly stable. That’s a regulated system. The idea that bodyweight is regulated has been around for 50 years and the subject of much debate. I’ll write about that at some later date, at this point simply accept that some level of regulation is going on.

The homeostatic system has to do with the idea that the body tries to maintain some specific ‘set point’ in terms of bodyweight or body fat. Basically this system takes incoming signal (from hormones like leptin, insulin, blood glucose, ghrelin, peptide YY and a host of other stuff) and makes adjustments in appetite, hormones, metabolic rate and activity to compensate.

The non-homeostatic system has less to do with internal signaling and more to do with how the body interacts with the external world. So when you are bombarded by food advertising, super size options (lots of food at a low price), appetizers (Awesome Blossom anyone?), and all you can eat buffets, these interact with the non-homeostatic system.

This paper basically lays out a quick review of the different systems before getting into the (complicated) neurobiology of how they work.

The homeostatic generally works better for defending against weight loss than weight gain. There are a bunch of complicated reasons for this, perhaps the simplest of which is that starving to death is very bad, while being fat was never really a bad thing in our evolutionary past. So the body developed a system to fight like hell agains weight loss but work fairly ineffectively against weight gain. Simply, for most people it’s far far easier to gain weight than it is to lose it. I’ll be getting into the details of this system as I continue to talk about leptin in coming issues but the above is the basic gist of it.

The non-homeostatic system has less to do with internal biology and everything to do with external environment. It also ties in with what is described as the hedonic system of eating: simply put, we eat because it is pleasurable. Essentially, the non-homeostatic system deals with issues related to food intake that are not governed by the homeostatic/internal system. The paper goes into the details, I don’t think they are that relevant for most readers, it has to do with how certain parts of the brain (the nucleus accumbens) “provide an interface between motivation and behavioral action.”

And this is where things get kind of interesting. One of the most eye-opening papers I may have read in recent years was by a research named Juan De Castro who looks at real-world eating habits (as opposed to what you might see in a lab or controlled setting). Basically he made the huge point that humans eat for reasons often totally unrelated to hunger. That is, it’s a convenient and easy trap to fall into to think of humans like rats: a gut and a nervous system with appetite being rigidly controlled by the set point. But it’s not that simple. Even rats can be fattened far past their set point with what is called a cafeteria diet (think cookie dough). Give them access to enough high calorie tasty food and they will over-ride any internal set point or homeostatic mechanism.

And the same holds for humans which a point De Castro made and which the non-homeostatic system appears to be involved with. The non-homeostatic system explains why so many humans appear to so easily override any internal homeostatic system that is operating. An abundance of food cues (tv advertising) and the easy availability of highly palatable calorie dense foods (would you like to Supersize that for only 39 cents?) and even the social environment all tend to promote food intakes far outside of any homeostatic system involved.

De Castro’s work has demonstrated this routinely. For example, the amount of food consumed goes up almost linearly with the number of people at an event. Now you know why you eat so much at holiday gatherings. People typically eat more on the weekends than during the weekdays. How much food is presented to you (all you can eat buffet anybody) also affects food intake: the more food on the plate, the more you tend to eat. So does greater food variability: the more variety at a given meal, the more people tend to eat. Think about the next time you are gorging on 18 different kinds of food at Thanksgiving dinner.

To quote one of his papers “Changes in intake can be detected with different levels of the number of people present, food accessibility, eating locations, food color, ambient temperatures and lighting, and temperature of foods, smell of food, time of consumption, and ambient sounds.” None of which has to do with any internally set system one bit.

But goes a long way towards explaining why restaurants (who are in the business of getting you to eat more) do what they do, and why most people in a modern environment have so many problems avoiding weight gain unless they impose a tremendous amount of self-discipline. It may also explain why bodybuilders and athletes, who are typically the most successful at dieting are succeeding: many of their behaviors explicitly avoid much of what De Castro’s work has demonstrated. By eating a low variety of food,s rarely if ever going out (many become social pariahs and refuse to go out with friends for fear of screwing up their near pathological eating patterns), avoiding most places where supersizing or buffet style eating would be a problem, etc they avoid many of the problems. Suggesting that type of approach (become a food obsessed hermit) to the non-obsessed is generally a recipe for disaster but recognizing that there are aspects of eating behavior that are not simply internally determined may be of some use. At the very least, recognizing those types of situations which tend to promote overconsumption is not a bad thing.

A point that I really want to drive home before wrapping this up is this:

I don’t want it to sound like these are completely separate pathways controlling food intake, which would be easy to do.

Rather, the systems are overlapping and integrated and separating them is more a function of convenience (and a reflection that they do represent slightly different things).

Here’s a quick example: the reward system in the brain is primarily dependent on dopamine. So the body releases dopamine in the brain in response to rewarding things (a bit more accurately, it turns out that it’s the expectation of rewarding things that releases dopamine) and this is what makes them rewarding.

Readers may have heard about the famous study were rats had a level wired up to fire the reward pathway in their little rat brains; they would sit there hammering away at the lever over and over, ignoring food, water, etc. That’s how powerful the dopamine/reward pathway can be.

Dopamine is also highly involved in addiction and addicting stimuli (such as drugs) tend to drive dopamine levels.

Now, one of the key hormones involved in the homeostatic system is leptin which I’ve been rambling about variously for damn near 10 years. Leptin does a lot of things in the body but, among them, arguably its primary role is as a signal to the brain about two things: how much fat you’re carrying and how much you’re eating on a day to day basis.

As it turns out, leptin appears to drive dopamine levels in the brain. When leptin drops, so do dopamine levels (this is discussed in more detail in my little book that most don’t even know about, on the drug Bromocriptine).

As it turns out, when you starve rats, they are more likely to become addicted to various substances, because of the drop in dopamine.

My point simply being that changes in the homeostatic system (for example, in response to fat loss or food restriction) are overlapping with the non-homeostatic (or hedonic) system. Everybody has noticed that food seems to ‘taste better’ when you’re hungry and these changes are probably why.

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