Newsletter #218 - The Gravitostat Theory of Weight Regulation 🍎
Hey guys! This week, I wanted to examine a hypothesis that I found really thought-provoking, known as the gravitostat. You probably already know that our fat mass is homeostatically regulated by the hormone leptin. Leptin is secreted by fat cells, and essentially tells the brain if you have enough stored body fat. More leptin suggests more body fat, and thus appetite will normally be reined in. However, this mechanism is usually disturbed in the context of obesity, and treatment with leptin unfortunately doesn’t really solve the problem.
More recently, researchers have proposed a second homeostatic mechanism that is independent of leptin, and instead hinges upon the force of gravity on our bone cells. We already know that osteocytes constantly respond to mechanical signals from the environment. This is why weight-bearing activity is associated with greater bone density, and why spaceflight results in profound loss of bone strength. And of course, body weight itself also affects bone mass - heavier people tend to have stronger bones.
Here's where things get interesting. Could mechanical signals also be activating a sensor that controls appetite and weight regulation? In other words, does increasing the force of gravity send a message to the brain through the bone cells that there is enough body fat (kind of like leptin), and in turn reduce food intake? And could this mechanism be exploited by adding artificial weight, like a weight vest, to effectively raise the set point?
I'm not quite sold on this, but it’s an intriguing idea in the context of the obesity epidemic and the way that we live now. The average office worker spends almost six hours a day sitting at their desk. Then you have to factor in that our leisure time activities tend to be pretty darn sedentary. In a sense, we are living in a state of attenuated stress from gravity, and this theory could shed further light on the association between sitting duration and risk of obesity.
This Week's Research Highlights
Since it is sort of hard to get rodents to wear weight vests (not that I've ever tried, I just assume it is), researchers in Sweden implanted capsules into the abdominal cavities of obese rats and mice that weighed 15% of the total body mass of each animal. Control animals were given empty capsules of equal size but that only weighed 3% of their body mass. They found that increased loading resulted in a reduced body mass, and that drop in weight was similar to the weight of the capsules. Furthermore, this was due to a decrease in food intake, rather than an increase in energy expenditure. To narrow down where this appetite-suppressing signal was coming from, researchers also tested the effects of weight loading in a special type of mouse that has been genetically engineered to have fewer bone cells (I know, sounds weird). Sure enough, osteocyte-depleted mice did not experience the suppression in body weight that animals with intact osteocytes had shown - suggesting that the gravitostat, if it indeed exists, works through bone cells.
Researchers recruited 72 participants with obesity (BMI of 30-35) and randomly assigned them to wear either a heavy (11% of total body weight) or light (1% of body weight) weight vest for eight hours per day for three weeks. At the end of the study period, the subjects wearing the heavy weight vest experienced a significant loss of body weight (-1.68%), while the control group did not. Importantly, this was caused by a reduction in fat mass specifically (-4.04%). Lean mass, on the other hand, was spared, which is pretty impressive since weight loss is almost always accompanied by loss of fat-free mass. The researchers were not able to identify whether this was due to changes in energy expenditure or energy intake.
If indeed the gravitostat regulates energy balance by picking up on changes in body weight, you would think that weightlessness would lead to greater body fat, right?
To test this, researchers at Oregon State University analyzed data from rodents that had been taken on spaceflight missions, and therefore were exposed to microgravity for prolonged periods of time.
They also simulated microgravity by “unloading” the hindlegs of rodents through a little harness that kept them dangling in the air. These decreases in gravity did not result in an increase in body mass. Furthermore, when they increased the force of gravity using a centrifuge, the animals did not lose weight. So I guess the jury is still kind of out on this hypothesis. That having been said, increasing energy expenditure through resistance or other means has been shown to help with weight maintenance, and weight bearing has been shown to improve bone density and even your brain, so there’s good reason to believe that this kind of intervention is beneficial, even if we’re still figuring out possible mechanisms.
Random Trivia & Weird News
According to the Cleveland Clinic, people with barophobia (from baros, meaning pressure or weight, and phobos, meaning fear) are irrationally afraid of the impact of gravity: that gravity might cause them to fall or that it might topple a heavy object onto them. This may also encompass a fear of microgravity or zero gravity.
Worth noting that this is associated with gravity specifically, and is distinct from basophobia (fear of falling) and acrophobia (fear of heights).
Podcasts We Loved This Week
- Stuart Phillips: Using science to build muscle and grow stronger. Via The Proof.
- Sarah Everts: The joy of sweat. Via Science Friday.
Products We Are Enjoying
If you’re thinking of experimenting with harnessing the gravitostat yourself, you probably need to get yourself a weight vest. This vest is very lightweight and unobtrusive (and cheap!), which is why I like it. Plus it’s got kind of a fun patriotic vibe with the stars and red stripes. But if you need something more formidable, there are all different sizes and weights out there - there are some adjustable vests that can accommodate more than a hundred pounds!
humanOS Catalog Feature of the Week
Thanks for reading, enjoy the weekend, and we'll see y'all next week!