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Homeostasis of Body Weight

Posted by tinako on July 3, 2010

Wait, wait!  It’s not as boring as it sounds!

I listened to a Yale Rudd Center podcast interview between Kelly Brownell, director, and Tamas L. Horvath, and found some of the points Horvath made so interesting I wanted to share them.

Tamas L. Horvath

Horvath is the Chair of Comparative Medicine and a Professor of Comparative Medicine, Neurobiology, and OB/GYN at Yale.  He does animal studies and particularly looks at the homeostasis of feeding and body weight, which is basically how different parts of the body interact with the brain to regulate what we eat and how much we store as fat.

He described synaptic plasticity, which means the brain can change to adapt to new environments, actually rewire itself.  For instance, if you eat a lot of carbs, the brain will increase aspects of brain function that increase energy expenditure and decrease appetite.  One way it does this would be by rearranging the connectivity between different circuits,  across different parts of the brain.  “Any time you change the environment, you will be changing connectivity of the brain.”

Brownell asked if these changes affect offspring, are they passed on to next generation?  Would an obese mother (from bad food environment) have different offspring than she would if she were thin?  Yes, Horvath said, the hormone environment to which the fetus is exposed is a major determinant of how the brain circuitry shapes.  You can skew metabolic regulation of the offspring by a pregnancy that is associated with diabetes, or for that matter, food types that are skewing the whole machinery.

I found this amazing.  One question that came to me was, we are told that 25-40% of body weight is a result of genes.  Did researchers account for this pregnancy environment mechanism, or would these effects be included within that number, even though they’re not genetic?

Brownell asked, if an overweight woman is pregnant and tries to lose weight, will the child be overweight because of the mother’s current status?  Horvath answered that the overweight status is not important, it’s the hormones present that are more important.  Hyperglycemia, etc., should not be present.  What’s in the mother’s blood is being communicated to the fetus.

This seems like very good news, because it means that an overweight woman who wants to spare her child this metabolism could help by, not losing all her weight before she gets pregnant (very difficult or too late), but by eating as well as she can for 9 months, and into breastfeeding I presume.

Brownell asked about the concept of a setpoint, a set weight to which our bodies will naturally return.  Horvath said yes, it makes sense that we have some sort of an optimal range in which we function best.  This setpoint is determined by communication between various tissues, environmental cues.  He said it’s difficult to put your finger on what exactly it is within the body.

Brownell asked if a setpoint is like a thermostat?  Is the body pretty good at regulating until the environment becomes unusual?  That is, processed food, high in fat and sugar and highly palatable, screws us up?  Yes, Horvath said, and sedentary lifestyles as well.

Brownell asked why it is so hard to lose weight, and Horvath’s answer was that you establish your base setpoint, and once established, it is difficult to shift downward (up is easy) – this is important for survival in scarcity.  Losing weight is going against a hardwired brain, very difficult.

Yes, Brownell persisted, but why does the body so fiercely defend obesity?  Why is the setpoint set high?  Why not keep the setpoint low and not kick in until the person becomes their ideal weight?  Brownell’s explanation sounded reasonable: in past times, the range of body weight was pretty small, no obesity, so body weight became irrelevant to triggering the defense, so it’s calorie deprivation that’s perceived by the body as a threat, no matter the weight.

Yes, Horvath said, why can you only move the setpoint up?  The working hypothesis is that in weight-gaining mode you might be killing cells responsible for satiety.  These cells are gone for good, no possible regrowth.

Horvath said our bodies are well-suited to environmental changes.  You can push the system and you will still maintain a weight, but if you keep pushing over time you will be shifting the setpoint.

I found both these explanations really interesting.  Horvath’s is obviously very discouraging for people who are already overweight.  I have to say that I have not heard very much good news from the professionals I’ve been listening to.

As an aside, I am very thankful that my mom once told me, when I was getting kind of pudgy, that it was important not to get carried away with weight, because once you gained it it was difficult to ever get rid of it, and it was much easier to not gain it in the first place.  Her explanation was that fat cells are created but never destroyed, they just empty, and subsequently they were much easier to refill than it was to create them in the first place.  I don’t know whether that is true, but whenever I approached my highest non-pregnant weight, I would catch myself and say, *no way* am I going higher.  On the other hand, for two years I have found it very easy to maintain a weight 20-25 pounds below that high weight, just through healthful eating, so that looks bad for Mom’s theory.  But I’m thankful because her advice did strongly motivate me to keep my pre-vegan habits in check.

Horvath talked a little about two areas he is studying, the effect on body weight of sleep and body/environmental temperature.

Brownell asked if Horvath was optimistic there will ever be helpful drugs, commenting that current drugs are only modestyly helpful, and as soon as people go off they gain the weight back.  Horvath said it is not good to rely on a pharmacological solution.  Prevention and education should play a bigger role.

Brownell said he agreed, the environment is so harmful no drug can undo that damage, but asked why not be more hopeful?  Why can’t somebody come across “the signal” to turn off?  Horvath anwsered, because there is no “the signal.”  It’s multiple signals.  Think of all the drugs people take that have side effects on weight.  The metabolic system is too complicated to reasonably expect we will understand it enough to regulate it with drugs.

Brownell asked about prevention and Horvath agreed it’s key, but unfortunately our culture does not promote real preventon; there’s no money there.  The money is in the pharmacological industry towards existing cases.  In many diseases this is reasonable, but less so for obesity and metabolic disorders, which are too complicated.

Brownell commented that changing the environment is daunting given how many bad influences there are.  He concluded that it was interesting that from their two different points of view, he from nutrition and public policy and Horvath from physiology, both agreed on how critical prevention is.  Brownell sees it in the clinic because they know how hard it is to lose weight and Horvath sees it from biological changes once an organism is overweight.


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