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An Appetite-suppressing Hormone in Bones

Researchers discovered, in a study in mice, that bones secrete an appetite-suppressing hormone called lipocalin 2 (LCN2). This hormone also regulates blood glucose (sugar) levels.

Building on previous findings that hinted at a possible role for bones in regulating appetite, the scientists searched for hormones produced in bone cells of mice and identified LCN2. This hormone had earlier been found to be made in fat cells and was associated with body weight. However, as shown in this study, compared to fat cells, bones produce much larger quantities of LCN2. To gain insight into the function of LCN2, the researchers explored what happens in its absence. They genetically engineered a group of male mice to be deficient specifically in bone-derived LCN2; these mice could still produce LCN2 in their fat cells. Without LCN2 from bones, these mice ate more than normal mice, gained more weight, and accumulated more body fat. The absence of bone-derived LCN2 also impaired blood glucose regulation. Thus, they concluded that LCN2 from bones normally dampens appetite and regulates blood glucose.

To confirm these results, the research team next studied the effects of excess LCN2. When they injected LCN2 into normal mice, the extra hormone reduced food intake, body fat, and weight. The researchers then found that levels of LCN2 naturally fluctuate with fasting and feeding. Delving deeper into how LCN2 affects appetite, the researchers discovered, in experiments in male and female mice, that LCN2 can travel to the brain, where it partners with another molecule, MC4R, to suppress appetite. An additional study revealed clues that LCN2 might work similarly in humans. Examining men with type 2 diabetes, the researchers found that higher levels of LCN2 in the blood correlated with lower body weights and better blood glucose levels.

This study highlights the importance of a bone-produced hormone in regulating appetite and blood glucose. Other research teams had previously identified LCN2 as playing a role in blood glucose control and other biologic processes, but had not detected its production in bones, and, curiously, had not observed any effects on appetite in mice. Further investigation may yield additional insights into the complexity of this hormone’s activities. If LCN2 suppresses appetite and improves blood glucose levels in people, it could potentially be targeted in the development of new therapies for type 2 diabetes and obesity.

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