University of Gothenburg researchers find that weight-bearing bones may help regulate body fat.
Do you use a standing desk at work? They’re popular in part because studies show higher risks of obesity, diabetes, and heart disease in people who sit for long periods. A recent PNAS study explored possible reasons why.
The work shows the value of informal knowledge-sharing among researchers in different fields. At Sahlgrenska Academy, University of Gothenburg, Professor John-Olav Jansson studies obesity and Professor Claes Ohlsson studies bone biology.
“The body must have a way to measure its own weight.”
“We were chatting about the clinical usefulness of knowing a person’s weight,” Jansson says, “and thought the body must have a way to measure its own weight.” Like a bathroom scale that you stand on, an internal scale should be low to be effective, so the scientists focused on lower-extremity bones, which are known to recognize load and respond by making more, stronger bone.
The researchers added weights to standard adult rats or mice with diet-induced obesity and found that both groups lost fat compared to control animals without added weight. Body fat changes were due to reduced food intake with probable contributions from energy burning. The effects were reversed when weights were removed and were independent of known weight regulators such as leptin, ghrelin, and glucagon-like peptide 1.
Since osteocyte bone cells sense load, the research team worked with mice that could be depleted for osteocytes. These mice did not show reduced body fat when weights were added to them, showing the dependence of the newly discovered weight-regulating system on osteocytes.
Homeostasis via gravitostat
Based on the results, Jansson, Ohlsson and their colleagues hypothesize a “gravitostat” system that uses lower-extremity, weight-bearing bones as a sensor, or scale. Osteocytes send signals based on the load sensed by the bones to change body fat to maintain a constant weight.
The discovery of a new physiological regulating system suggests many directions for future studies. Jansson says they are continuing to investigate interactions between the gravitostat and leptin systems. They are working on the mechanisms and biochemical details of gravitostat homeostasis and are talking about how to design a clinical trial in humans.
For people thinking of walking around with a weight vest or working at a standing desk, Jansson notes that lots of time sitting is linked to health risks. He’s careful, though, to state that gravitostat results are early and so far only in rodents.
“We have a model that indicates a setpoint for body weight,” he says, “but it’s a working hypothesis that’s not proved yet.” Jansson says people tell him they are going to carry weights and see if they lose weight. “That’s fine,” he says, “but we need to learn the gravitostat mechanism and do a real clinical study.”
Jansson JO, Palsdottir V, Hägg DA, Schéle E, Dickson SL, Anesten F, Bake T, Montelius M, Bellman J, Johansson ME, Cone RD, Drucker DJ, Wu J, Aleksic B, Törnqvist AE, Sjögren K, Gustafsson JÅ, Windahl SH, Ohlsson C. Body weight homeostat that regulates fat mass independently of leptin in rats and mice. Proc Natl Acad Sci USA 2018;115(2):427-432.