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Exploiting the “gravitostat,” a novel homeostatic mechanism that regulates body weight, promotes weight loss.

Having overweight or obesity increases a person’s risk of developing many chronic diseases. But losing weight loss is challenging, partly due to homeostatic mechanisms that regulate body weight. Findings from a 2020 study suggest that exploiting a novel homeostatic weight-regulating mechanism called the gravitostat promotes weight loss in humans.

The concept of the gravitostat first emerged in 2017, when scientists implanted small weights into the abdomens of mice and found that the animals’ food intake decreased, promoting weight loss and improving glucose tolerance. They suggested that the gravitostat regulates weight via a negative feedback system involving bone cells called osteocytes. Because osteocytes can sense changes in bone strain, the investigators proposed that increasing the animals’ body weight activated a biological sensor that communicated with the osteocytes of weight-bearing bones to drive changes in eating behaviors and subsequent weight loss.

In the 2020 study, the investigators conducted a randomized controlled trial involving 69 adults with mild obesity (body mass index of 30-35). About half of the participants wore a heavy weighted vest (11 percent of their body weight) for eight hours every day for three weeks, while the other half wore a light vest (1 percent of their body weight). Before and after the intervention, the investigators weighed the participants and analyzed their body composition using bioelectrical impedance.

They found that participants who wore the heavy vest lost an average of 1.37 percent more bodyweight than those who wore the light vest, translating to about 3.5 pounds. Those who wore the heavy vests also lost fat mass and gained fat-free mass. These findings suggest that the gravitostat regulates body weight in humans and exploiting it provides a possible strategy for losing weight.

Overcoming other aspects of bodyweight homeostasis might still prove challenging, however. Research from Dr. Eran Elinav’s lab suggests that metabolic parameters normalize with weight loss, but characteristics of the microbiome remain unchanged. In other words, the microbiome holds a memory of past obesity that promotes weight regain. Preclinical studies indicate that repeated weight cycling shifts gut microbes to a configuration with an altered ability to metabolize flavonoids — compounds that usually help promote the burning of excess energy by adipose tissue. Learn more in this clip featuring Dr. Eran Elinav.

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