Why bones might hold the secret to weight loss

Scientists have found an entirely new mechanism by which our body measures and influences our weight. This "gravitostat" is thought to reside in our bones and may offer new treatment avenues for obesity.

In recent years, the link between spending long periods of time sitting down and obesity have been confirmed repeatedly.

Extended periods of sedentarism may even increase the risk of death from all causes.

The interaction between prolonged sitting and obesity does not seem particularly surprising; obesity follows naturally from less exercise.

However, some studies have shown that the relationship between hours spent sitting and obesity are independent of the amount of exercise undertaken.

In other words, standing itself seems to have anti-obesity powers beyond the number of calories it burns.

Recently, a group of researchers from the Sahlgrenska Academy, at the University of Gothenburg in Sweden, looked into a novel mechanism that might, in part, explain these findings.

A new fat regulatory mechanism uncovered

A hormone called leptin is involved in regulating body fat. When it was first discovered, there were high hopes that it might help to treat obesity. Since leptin's discovery 23 years ago, no other body fat regulatory system has been found — until now.

As Prof. John-Olov Jansson, of the Sahlgrenska Academy, states, "Quite simply, we have found support for the existence of internal bathroom scales. The weight of the body is registered in the lower extremities. If the body weight tends to increase, a signal is sent to the brain to decrease food intake and keep the body weight constant."

To come to this intriguing and important conclusion, the research team ran a series of experiments on rodents (both rats and mice). The animals were implanted with weighted capsules, making them 15 percent heavier. Control animals had empty capsules implanted, increasing their body weight by just 3 percent.

Amazingly, the animals carrying the additional weight reduced their food intake to compensate. Over the course of the experiment, the animals lost roughly the same amount of weight as was added by the artificial load.

Body fat decreased, and blood glucose levels improved. Motor activity was unchanged, meaning that the loss of fat was solely due to dietary changes.

To understand whether or not leptin could be behind this fat loss mechanism, the team repeated its experiments on a strain of mouse that does not produce leptin. In these mice, the results were the same, implying that leptin is not responsible. This is an entirely new mechanism.

Their findings are published this week in the Proceedings of the National Academy of Sciences.

How can the body weigh itself?

The answer appears to be in our bones. Osteocytes, the most common cell type in bone tissue, are important for communication between cells. Osteocytes can detect whether a particular section of bone is under increased mechanical stress, signaling the need for new bone formation and remodeling.

The researchers carried out the same experiment again, but this time using mice with reduced numbers of osteocytes. They found that the animals no longer lost weight in response to the weighted implants. The mechanism appears to be osteocyte-dependent.

They conclude that "increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal [a signal going to the central nervous system], which reduces body weight."

Because this is the first time that our internal weighing scales — or the "gravitostat," as named by the researchers — have been glimpsed, there is a vat of follow-up work that needs to be done. Regardless, the potential ramifications are exciting.

"We have discovered a completely new system that regulates fat mass. We hope this discovery will lead to a new direction in obesity research. The findings may also provide new knowledge about the cause of obesity and, in the long run, new treatments of obesity."

Prof. John-Olov Jansson

Claes Ohlsson, who is part of the study group, hopes that the new system might be exploited alongside leptin. He says, "The mechanism that we have now identified regulates body fat mass independently of leptin, and it is possible that leptin combined with activation of the internal body scales can become an effective treatment for obesity."

Many unanswered questions

Uncovering a new mechanism unearths many more questions than it answers. For example, if osteocytes are involved, how exactly do they exert their influence on feeding behavior?

To attempt to answer this question, the team looked at a range of bone-derived compounds, including sclerotin and osteocalcin, but none seemed to be involved.

They also explored the potential roles of other factors involved in fat regulation, including ghrelin (a hormone involved in hunger), MC4R (an important mediator in the effects of leptin), and estrogen receptor-alpha (involved in regulating fat and bone mass). None appeared to play a part.

Understanding how an internal weighing system might work could help to unravel the connections between sitting time and health. Ohlsson explains, "We believe that the internal body scales give an inaccurately low measure when you sit down. As a result, you eat more and gain weight."

Although there are many questions that remain and need to be answered, the results of the new study are fascinating. Potentially offering a new direction for obesity research, the findings are likely to spark debate and discussion among medical scientists far and wide.