Rec
ently several folks have asked us questions about diet, hunger, weight gain, and nutrition.
Certainly for many people with depression, gaining weight is an important issue, both as a cause and consequence of depression.
Let’s begin by trying to make some sense of hunger. In other posts we will be talking about how stress and the hormone system relates to diet, hunger and weight gain. We will also talk about what influences how many calories we burn. And finally we will talk about how diet affects weight. .
Regulating how much we eat is a basic function of the human brain and body and the systems that have developed to maintain our body weight are remarkably effective. Unfortunately, they may not be as well adapted to modern life, with instant access to unlimited highly dense foods, as they were to our distant past when there was an ever-present risk of going hungry.
There are a few key hormones that are involved in regulating hunger and satiety –
- Leptin
- Ghrelin
- Neuropeptide Y
- Melanocyte Stimulating Hormone
- Cortisol – which we will discuss in another post.
Leptin is a hormone that is tightly regulated by how much body fat you have. As you put on fat there is more and more circulating leptin. And low leptin is a trigger for various behaviors designed to allow you to gain weight.
However, leptin is best not thought of as primarily a weight regulating hormone. It is a hormone that is primarily designed to encourage maintaining enough weight that it is safe to have children. At very low levels of leptin, people are incredibly hungry (low leptin is one of the strongest triggers for hunger) and their reproductive system is shut down, until a normal body weight is reached. In other words, low leptin shuts down the reproductive system and drives us to eat enough so that can be ready to have children. Then, as we gain fat, our leptin levels increase. But for some of us we remain hungry as we become obese, even though our leptin levels are very high. There are a number of theories about this. One suggests that, just as we can be insulin resistant when we begin to have diabetes, we can be leptin resistant as we get fat.
To confuse things further, leptin may also be involved in anxiety regulation. High levels of leptin may be 
associated with lower anxiety (perhaps the reason why overeating can be helpful, in the short run, as a way of dealing with anxiety). In other words, our brains may be conditioned to reach as high a level of leptin as possible, a strategy that might have made sense when scarcity was the norm, but might be part of the reason for the obesity epidemic we face.
Think of leptin as the “Big Momma” hormone. Designed to make you feel secure and enabling you to have a family safely in a world where not having enough food is always a possibility. But perhaps not your friend in a world where starvation is rare.
Ghrelin is a hormone that does two things – it increases the release of growth hormone and it increases food intake. If leptin is the “Big Momma” hormone, ghrelin is the big strong person hormone. Unlike leptin, where low levels stimulate appetite, ghrelin works the other way, high levels of ghrelin stimulate appetite, and it has both short term and long term effects. In the short term, it is part of what drives hunger as you get close to meal time, in the long run, it appears that ghrelin is part of the problem many of us wrestle with after we lose weight. It now appears that our bodies keep trying to return to the former (unhealthy) weight for at least five years, and perhaps indefinitely. And ghrelin is involved in the long term problem of increased hunger when you get down to a healthy weight.
Neuropeptide Y is one of the most potent stimulators of appetite known. It is also involved in regulating a number of aspects of the stress response system. Just as with leptin, neuropeptide Y affects both anxiety and appetite. Unlike leptin, high levels of neuropeptide Y are associated with reduced anxiety (perhaps including reduced PTSD symptoms) and increased appetite. There is a very close relationship between neuropeptide Y and the stress system (cortisol, cortisol releasing hormone) and some of the effects of neuropeptide Y may be indirect, due to how it affects the stress or cortisol system.
Melanocyte Stimulating Hormone is perhaps the most mysterious of these hormonal influences on appetite. In fact, MSH is named because of its effects on skin pigmentation (it stimulates melanocytes, which are the cells that lead to darker skin when tanning). However, it turns out that MSH is also involved in regulating appetite and sexual behavior. MSH inhibits food intake. And animals without the MSH system intact become morbidly obese. How this relates to humans is less clear. Stay tuned to new stories about how this system may be involved in the human obesity epidemic…
In summary…
Our brain and body developed in a time where the main challenge was gaining enough weight so that we could grow strong and have children. It did not really develop to help us deal with too much food, and particularly too much high density food (food with lots of calories and little fiber).
Our body and brain remain fixated on making sure that we are getting enough food, and thus we need to think about strategies for living that do not expose us to too much temptation (high calorie foods).
In this area, as in so many other areas of medicine, it is much better to prevent obesity than it is to try to get back to a normal weight. Once you have become obese, parts of your brain will try to take you back to obesity for a very long time.
There is a very intimate relationship (as if you didn’t know this already) between stress response systems, reproductive systems and appetite regulating systems. This may be part of why it has taken so long to come up with good treatments for obesity. Things that reduce weight are not hard to find, but those things tend to disrupt other extremely important body functions.