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Homeostatic and Non-Homeostatic Pathways and Food Intake

I don’t know how much the readers of my site care about the depths of neurobiology, although I wouldn’t be surprised if I had some given how I write or what I write about.  In any case, this is somewhat technical article where I want to look at what are called the homeostatic and non-homeostatic (or hedonic) pathways and how they impact on food intake.

The very simple distinction between the two is that the homeostatic system is involved in regulating food intake based on the body’s actual needs whereas the non-homeostatic/hedonic system is based on environmental factors and the fact that food tastes good.  Now let’s look at the complex distinction.  First let me start with a couple of definitions.

Regulation

The idea of regulation means that, well, a system is regulated.  Ok, that doesn’t help.  What this means is that a system has some way of attempting to keep itself at a fairly consistent level.   This requires a couple of things.  The first it some way to set the system where you want it.  But there also has to be a way of measuring inputs from the real world.

An easy example is the air conditioning or heat in your house.  So you set it at some temperature that you want to keep your house at.  In an ideal world this means that the temperature would stay at that level without change but we know that’s not how it works.

Rather, what you will see is that the temperature will increase and the thermometer will sense this.  This will trigger the device to turn the air conditioning on.  Now the temperature will drop but invariably it will overshoot the goal temperature and get a little bit too cold.   The thermometer senses this as well and the air turns off to let the temperature come up naturally.  Or the heat turns on.

At this point the air turns off and either the temperature comes back up or the heat turns on.

If this is unclear think about a cruise control in a car.  Here you set a speed which the car should ideally maintain.  But it doesn’t work that way.  Rather, if you start to slow down going up a hill, the speed sensor will “notice” and put more gas into the engine.  If you start going too fast, it will put in less.

Simply, those systems are regulated in that they are attempting to maintain a given setting by allowing feedback by comparing external signals (temperature, speed) via some measurement device (thermometer, speed sensor) to attempt to maintain the system at some defined point.

The following image comes from my Guide to Flexible Dieting and shows the basic idea of a regulated system.

Diagram of a Regulated System

Homeostasis

In the body, the idea of regulation is often referred to as homeostasis.  Here the body is trying to maintain some physiological system at a relatively fixed level and it does so in very much the same way as the thermostat or cruise control.

So consider body temperature.  Under normal conditions, the body will try to maintain temperature at some level such as 98.6 F (37  C).   If body temperature starts to go above this level a number of things will occur.  Blood vessels will dilate and the body will start to sweat to try to dissipate heat and reduce core temperature back to the baseline level.    If body temperature falls in the cold, a number of things occur.  Blood vessels constrict so there is less blood flow to the extremities.  You also start to shiver so generate heat through muscular activity.

The same is seen in endless other systems.  If blood glucose falls, the body will release glucagon to mobilize glucose from the liver along with the drop in insulin causing a release of fatty acids to provide energy.     Blood pressure is regulated and there are tons of others.

Allostasis

For nothing more than completeness, let me mention the concept of allostasis.  The idea here is that there are rarely singular setpoints and/or that they can change.  So working from the body temperature, consider getting a fever.  Here, for various complex reasons, the body’s temperature setpoint is raised above normal.  So now it’s 99.6F (37.5 C).  But while that body temperature would normally cause sweating, it doesn’t here.  Because this is now the goal temperature.  Women experience something similar during the second half of their menstrual cycle when their temperature may increase by 0.5 F (0.3-0.6C).

Overcoming Homeostasis

Whether we focus on homoestasis or allostasis, these all represent regulated systems.  First there is a target setpoint, body temperature (blood glucose, blood pressure) along with some sort of sensor in the body.  When a change occurs the sensor will cause alterations in body physiology in an attempt to bring the body back to some setpoint.

But there is another factor: homeostasis can often easily be overwhelmed.  So consider the situation where someone is exercising in a very hot and/or humid environment.  As their core temperature goes up, they will dilate blood vessels and start to sweat.  But if it’s too hot or too humid, this won’t be sufficient to cool the body.  Core temperature will continue to go up as the body desperately attempts to compensate but it can’t keep up.  Eventually the body becomes overwhelmed and the system shuts down completely.

The same occurs in the cold.  If it’s chilly, shivering and vasodilation can keep core temperature from falling too far.  But as it gets colder or the exposure longer, the body can’t keep up.  At the minimum, you start to see things like frostbite where fingers or toes die due to too little blood flow.  At even further extremes, the person freezes to death.

So the key points are this:

  1. Many if not most systems in the body are regulated, at least attempting to maintain some relatively stable level.
  2. That stable level can change and become the new “setpoint”.
  3. Those systems can often be overwhelmed by extremes in the external environment.

Which is a long way to get to the actual topic.

Bodyweight Regulation

I’ve been writing about the topic of body weight regulation for a majority of my career.  The idea is that human body weight is regulated in the sense of the body attempts to maintain a certain weight or perhaps body fat percentage.     Usually this supposed goal weight/BF% was called the setpoint.   This would be the body’s equivalent of the temperature you put your thermostat at.

The data on this originally came out of rat and mouse research.  Here it was routinely found that both would maintain their bodyweight at extremely exacting levels.  If you overfed them and they gained weight and fat their appetites would shut down and they would become more active.  As soon as the overfeeding was taken away, they would rapidly return to their previous weight.

The same happened if you dieted them/starved them.  Their metabolic rates would go way down and they would become much less active (called torpor) to conserve calories.  As soon as food was available they’d start eating again until they re-achieved their original bodyweight at which point they would return to normal and stabilize.

But it’s fairly clear that in animals the system is pretty carefully regulated.  In an evolutionary sense this is logical. For a rat being too lean means starving to death.  But being too fat means being something else’s lunch.  It was important in that situation for the animals to avoid either extreme if at all possible.

But there’s another important aspect here: in the right environment, when you give rats and mice access to what is called a cafeteria diet (think of this basically as chocolate chip cookie dough) in a cage they will become obese and the regulated system is overwhelmed.  Just keep that in the back of your mind for a second: extreme environmental factors can readily overwhelm any built in system of regulation.

Is Human Bodyweight Regulated?

But the idea that humans maintain a specific setpoint has been an issue of contention for decades now.  Depending on what review paper you read there either is evidence for it or isn’t evidence for it.  All it takes is to carefully select which studies you pull.

Most of these studies tend to be indirect and what is usually being looked at is adaptations in things such as energy expenditure or appetite.  And simply put, those adaptations are well established.   As I’ve also been writing about for nearly 2 decades now, it’s well established that the body adapts to fat loss.  All four components of energy expenditure decrease, appetite increases and there are multiple other adaptations that are occurring.

Perhaps the most extreme example of this is the seminal Minnesota Semi-Starvation study.  Here war objectors were placed on 50% of maintenance calories, dieting to the extremes of low bodyfat.  When food was made available their appetites stayed high until they had achieved their initial weight and body fat percentage and then overshot it.

All of this suggests that there is some sort of biological setpoint below which the body adapts to try to pull weight and body fat back to the starting level.

The Homeostatic System

And all of that points to what is usually called the homeostatic system. Simply, the body, via the hypothalamus “monitors” endless incoming signals regarding things like body weight, bodyfat percentage, muscle mass, blood glucose levels, amino acid levels, fat levels, etc.  Hormones such as leptin, ghrelin, PYY, CCK and others all send this integrated signal to the hypothalamus which makes adjustments to the rest of the body.

So when you diet, the hormone leptin drops.  This signals to the brain both that you’re eating less and losing body fat.    This causes adaptations in endless hormones.  Leptin controls FSH/LH which control reproductive hormones.  Leptin impacts on CRH which controls cortisol release and cortisol goes up, possibly contributing to water retention on a diet.  Leptin controls TRH which impact on thyroid hormone release.  It also controls nervous system output which goes down.

There are endless other adaptations, all of which tend to slow metabolic rate and energy expenditure, decrease fat oxidation, increase appetite, etc.  There is clearly some form of homeostatic system that at least attempts to regulate body weight.  At least in terms of making fat loss difficult.   I’ll come back to this.

Set Points or Settling Points

At the same time other still disagree with the setpoint idea.    Rather, they argue that there is a settling point that is created by the interaction of environment.  So we know that if someone changes their diet and activity patterns, they will generally lose some amount of weight and fat and then stabilize at the new level.  They have settled at that point.

So far as I’m concerned, they are both right.  Within some range of body weight and body fat, about 10% in either direction, there is no clear evidence of a setpoint, it’s purely environmental.  But once you get outside of that range, you see clear metabolic adaptations which attempt to pull the body back to where it was.  The mistake both groups made is in thinking it has to be one or the other.  Instead, a model where settling point predominates in a certain range with set point becoming more prevalent outside of that range encompasses all of the extant data.

What About Fat Gain?

But there is another problem with the setpoint idea which is this: while the body seems to resist fat loss pretty well, it certainly doesn’t seem to do a very good job at preventing weight and fat gain.  This is a point that the folks who disagree with the set point idea bring up a lot.   The obesity epidemic continues to increase by the year.  Clearly the idea that there is some rigid homeostatic setpoint in place would seem to be flawed.

Now, there are at least some adaptations that occur with overfeeding and fat gain.  Total energy expenditure often goes up a little bit although it’s not nearly enough to offset the calorie surplus.   In at least some people, Non-Exercise Activity Thermogenesis (NEAT) increases which helps to limit fat gain.  But it’s only in a percentage of folks. Discussing the reasons for this individual variance would take another article.

But those effects seem to be short lived.  And it’s clear that in the majority of people, the effects don’t accomplish very much.

There are multiple possibilities why this might be the case and this isn’t the place to go into them here.  Rather I think it’s more informative to go back to the animal research.  Recall what I mentioned above.

  1. Rats and mice tend to die if they get too lean (starvation) or too fat (predation).  They have a strict setpoint.
  2. The right environment can overwhelm that strict setpoint.

Briefly about number one.  Humans, by and large have no predators.  So in contrast to animals who get eaten if they get too fat, there was no real selection pressure against becoming obese.  Additionally, even the health issues that accompany obesity don’t show up for decades which means that reproduction was not hindered.  So they couldn’t be selected against in an evolutionary sense.

But number two is really the key point.  Even animals with a strictly regulated homeostatic system can have it become overwhelmed by the right environment.  Specifically in this case, with tasty delicious food.

The Non-Homeostatic/Hedonic System

Which brings me the long way around to the non-homeostatic/hedonic system.   This has essentially nothing to do with any internal signals of food intake, etc. that are inside the body but everything to do with the environment.   And while this sounds basically like the settling point concept it is and it isn’t.  This is more to do with the biological systems controlling some of how you interact with the environment.

More to the point, it’s less about what you choose to do with your food intake and activity and more to do with how environmental factors can drive food intake despite what the homeostatic system is signaling.

Here’s an easy example: you’re at Thanksgiving dinner.  You’ve just eaten your fill of turkey, stuffing, etc.  You’re full to the point of being nearly sick.  You couldn’t eat another bite.  Then someone offers you this:

Gooey Chocolate Cake

And suddenly you’re just hungry enough to eat a piece or three.

That’s the non-homeostatic/hedonic system in a nutshell.  It represents the fact that environmental food cues can drive hunger or desire to eat something whether someone is truly biologically (in a homeostatic system sense) or not.

So at the mall food kiosks will waft delicious sensory smells through the air, driving appetite.   Super sized options where you get more food at a lower price tend to drive overconsumption as well.  Appetizers, all you can eat buffets, pictures of delicious foods and endless other factors can drive food intake far beyond what the homeostatic system should allow in theory.

Simply, we don’t just eat because we are hungry or full.  We also eat because it’s pleasurable.   

Of course, humans also eat for a lot of other reasons.  We eat out of boredom, eat due to stress, or eat for seemingly irrelevant reasons.  In one of the more fascinating papers I ever read, Juan DeCastro wrote about real world human eating patterns.  Among them he noted that most eat more on the weekends during the week.   We also tend to eat more food if there is more food on the plate.  But fascinatingly there is a strong relationship between the number of people at a meal and food consumption.  The more people present, the more people eat on average.

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.  Mind you, these are factors restaurants leverage to get people to eat more.  Which is kind of part of the problem.

It also probably partly explains why bodybuilders and obessed athlete are often the most successful dieters: their behaviors explicitly avoid most of what De Castro’s work has shown to occur.  They eat a low variety of foods, become social pariahs who never go out with friends or family, avoid places where they are even faced with the option of supersizing or having the hedonic system take over would be an issue.

It’s easy to fall into the trap of thinking humans are like rats, that we are just a gut and a nervous system with appetite (and by extension body weight and body fat) rigidly controlled by a setpoint.   But we aren’t.  Even rats, as I mentioned, can be reliably fattened with the cafeteria diet.  Give them something delicious enough that is easily available and that will overwhelm any internal setpoint of homeostatic mechanisms.

The Neurobiology of the Hedonic System

I’m actually going to skip most of the complex details of the non-homeostatic system in terms of how it works.   When you get deep into this literature you start getting into details of the nucleus accumbens, amygdala and the distinction between wanting and liking.  Both the opiod and endocannibanoid systems play a role.  It’s very complicated.

But one of the key players here is dopamine (DA) which I imagine most know of as the reward system.  Basically when you do thinks that feel good dopamine is released and this signals reward.   Most enjoyable things drive dopamine.  Buying fun stuff, sex, gambling, eating.  They all drive dopamine.   So eat that piece of gooey cake and dopamine goes up.

Gooey Chocolate Cake
                  You know you want it

 

Readers are probably familiar with a famous older study where rats were wired up so that their DA system would get stimulated if they hit a bar.  And the little buggers would sit there hammering away at it over and over ignoring food, water and the rest.  If you’ve ever seen someone sit at a slot machine for what seems like days putting money into it, you have a pretty good idea of how powerful the system can be.

But it’s even more complex than this.  Initially, dopamine is a signal of reward, it goes up when you get the reward.  But after some time dopamine goes up as an expectation of reward (this is how you train dogs).  Now seeing a tasty food that you like raised dopamine which tends to make you want it even more.  And this is assuredly part of how the hedonic system is working.

I’d note that dopamine is highly involved in addiction.   An interesting tidbit is that habitual drug users DA levels will go up before even using their drug of choice.  The entire ritual of their use, whether it’s rolling a blunt or tying off a vein, drives DA in expectation of the high.

Food intake works through the same systems and there have been many comparisons between overeating hyperpalatable foods (think high sugar, high fat, cheap and readily available foods) and drug abuse.

Because after you’ve learned that something is delicious, simply being exposed to it on some level, even smell or sight, can raise dopamine levels in expectation of eating it.  That increased DA level will drive desire.  And that’s when you enjoy that cake.

The Systems Overlap

Let me finish by pointing out that the homeostatic and non-homeostatic/hedonic systems should never be considered as distinct and isolated anymore than any other system in the body.

As a singular example, let me go back to leptin. Among its other roles, leptin controls dopamine levels in the brain.  As leptin levels fall during a diet or with fat loss, so do dopamine levels (this was the basis for my idea of using Bromocriptine, a dopamine agonist on a diet).

And inasmuch as dopamine is involved in the reward system, this means that falling leptin will cause the non-homeostatic/hedonic system to work even more effectively.  One of the adaptations to dieting is that people become more “attuned” to tasty foods.  They notice them more.  They also taste better than when someone is full.  I mean, ok they taste great when you’re full.  But the experience is damn near orgasmic when you’re really hungry.

Acknowledging the limitations of animal research, rats are more likely to become drug addicted when they are starving.  This is due to basal dopamine levels being lower so that the “high” of the drug hits that much harder.

But I’m off topic.  The major take home points of this article are this:

  1. There are two primary systems controlling food intake in humans
  2. The homeostatic system is involved with internal biology, using signals such as leptin, ghrelin and many others to impact on factors such as metabolic rate and appetite
  3. The hedonic system is about reward and is driven by the environment. It involves many neurochemical pathways but basically occurs because food is tasty
  4. While there is evidence of a setpoint in the sense of the body adapting biologically to changes in food intake and body weight/bodyfat, it works best to defend against fat loss
  5. Because when it comes to fat gain, it’s clear that in all species, environments providing lots of easily accessible hyperpalatable foods can readily overwhelm the homeostatic system by co-opting the non-homeostatic/hedonic system.

And now hopefully you know something you didn’t yesterday.  And you’re probably hungry for cake.

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