3:30 PM
 | 
Mar 16, 2017
 |  BC Innovations  |  Targets & Mechanisms

Bone appétit!

How a bone hormone could help treat obesity

Last week’s Nature publication of a hormone secreted by bone that suppresses appetite and can curb weight gain not only adds to the emerging picture of bone as a player in the endocrine system but establishes a bone-brain axis as a new way to treat obesity.

Osteoblasts - the cells that make bone - are now recognized as major players in bone biology, with the ability to both make and release hormones. They are thought to play a role in metabolism because they secrete osteocalcin, which promotes energy expenditure, insulin secretion and glucose homeostasis, and FGF23, which regulates phosphate metabolism in the kidney.

Now, a group from Columbia University has added a third hormone to the list, LCN2, and shown it activates MC4R, a brain receptor that suppresses hunger by making people feel full.

Principal investigator Stavroula Kousteni told BioCentury that while the role of MC4R in satiety was well known, no one knew LCN2 was a ligand for the receptor, or that it was produced by bone. According to the study’s authors, mutations in MC4R account for up to 5% of cases of childhood obesity and 0.5-2.5% of cases of adult obesity.

“This discovery may be one of the first mechanisms uncovered for communication between lean body mass and the brain.”

Roger Cone, UMich

Kousteni said that prior to her group’s findings, LCN2 was primarily considered a pro-inflammatory signal made by fat cells. “Its expression was never looked at in bone.”

“What we found was that under basal conditions - not inflammatory conditions - LCN2 is expressed in osteoblasts at at least tenfold higher levels than in any other tissue, including adipocytes,” said Kousteni, who is an associate professor of medicine in...

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