Although it is known that osteocalcin affects how we metabolize sugar and fat, how it works was unknown until recently when Mathieu Ferron, a researcher at the Montreal Clinical Research Institute (IRCM) and professor at Université de Montréal's Faculty of Medicine, published his latest osteocalcin-related research in The Journal of Clinical Investigation.
Osteocalcin is produced by osteoblasts, the same cells responsible for making our bones. The hormone builds up in bone, and then, through a series of chemical reactions, is released into the blood. The IRCM team has focused on this key step.
"When it is first produced in osteoblasts, osteocalcin is in an inactive form," Ferron noted. "What interested us was understanding how osteocalcin becomes active so as to be able to play its role when released into the blood."
The IRCM lab demonstrated that an enzyme, which acts like molecular scissors, is required. Inactive osteocalcin has one more piece than active osteocalcin. The researchers examined in mice the different enzymes present in cells where osteocalcin was produced that could be responsible for snipping off the piece in question.
They found that furin causes osteocalcin to become active and the hormone is then released into the blood. "We demonstrated that when there was no furin in bone cells, inactive osteocalcin built up and was still released, but this led to an increase in blood glucose levels and a reduction in energy expenditure and insulin production," Ferron said.
Deleting these "scissors" also had an unexpected effect: it reduced the mice's appetite. "We're confident that the absence of furin was the cause," Ferron said.
Indeed, his team demonstrated that osteocalcin itself has no effect on appetite. "Our results suggest the existence of a new bone hormone that controls food intake," Ferron said.
"In future work, we hope to determine whether furin interacts with another protein involved in appetite regulation."
Image courtesy of Wikimedia Commons.