A hormone secreted by bone cells can suppress appetite, according to mouse studies. The hormone--called lipocalin 2--turns on neurons in the brain that have been previously linked to appetite suppression. The findings reveal a previously unknown mechanism for regulating the body's energy balance and could lead to new targeted therapies for the treatment of obesity, type 2 diabetes, and other metabolic disorders.

The study was published in the journal Nature.

In the current study, the researchers demonstrated that FOXO1-deficient osteoblasts express unusually high amounts of a protein called lipocalin 2. Lipocalin 2 was previously thought to be primarily secreted by adipocytes (fat cells) and to contribute to obesity. But the researchers showed, using mice that could not produce lipocalin in either their fat cells or osteoblasts, that lipocalin 2 is primarily secreted by osteoblasts and reduces appetite and weight.

Lipocalin 2 also affected appetite and weight in normal-weight mice and in mice that were obese due to a lack of the leptin receptor and leptin signalling. In both types of mice, lipocalin 2 suppressed appetite, improved overall metabolism, and reduced body weight.

The team also found that lipocalin 2 crosses the blood-brain barrier. In the brain, the protein binds to and activates melanocortin 4 receptor (MC4R) neurons in the hypothalamus, the primary brain region that regulates appetite. MC4R neurons are known to be involved in triggering appetite suppression.

"The hope is that lipocalin 2 might have the same effects in humans, and that our findings can be translated into the development of therapies for obesity and other metabolic disorders," said the senior author.

Initial findings in humans are encouraging. In an analysis of patients with type 2 diabetes, the researchers found that blood levels of lipocalin 2 were inversely correlated with body weight and blood A1c levels, a long-term measure of blood sugar. "In other words, patients with higher lipocalin 2 levels had lower body weight and better glucose balance," said the senior author.

http://newsroom.cumc.columbia.edu/blog/2017/03/08/bone-derived-hormone-suppresses-appetite-in-mice/

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature21697.html