In addition to providing structural support, the skeletal system aids in hormone production, making it an unexpected player in the endocrine system. Shown to emit hormones that regulate kidney and glucose homeostasis, bones ultimately promote the regulation of energy metabolism. However, a recent study at Columbia University has proven that hormones secreted by bones may also play a part in appetite suppression.
The study was motivated by an observation by Dr. Stavroula Kousteni and her team. According to Kousteni, “studies from our laboratory had shown that mice lacking 50 percent of their osteoblasts, cells that facilitate bone formation, had an increase in appetite. So, we initiated a search for a protein secreted by osteoblasts that would regulate appetite.”
Lipocalin2, or LCN2, is a hormone linked with obesity that has been previously thought to be secretly exclusively by adipose tissue, or fatty body tissue. However, it has been discovered that osteoblasts, or cells that aid in the synthesis of bone, secrete LCN2 by ten-fold in comparison to adipose tissue.
Image credit: Henry Vandyke Carter
To examine the effects of this discovery, the research team curated two mouse lines: one that did not secrete LCN2 in their osteocytes, and one that did not secrete LCN2 in their adipocytes. Although LCN2 proteins secreted by osteoblasts and the adipose tissues were identical in structure, only mice with inhibited osteoblasts exhibited decreased islet numbers, cell sizes, β-cell mass, and β-cell proliferation, which led to decreased glucose tolerance and insulin secretion. Ultimately, these differences manifested in an increase in total fat mass of 19.6%, and an increase of 5% in body weight from the control. These mice also demonstrated a 16.4% increase in food intake. The mice that failed to secrete LCN2 hormones from adipose tissues did not show changes in fat or body weight.
Kousteni’s team also found that after a meal, LCN2 is secreted from the bone’s osteoblasts directly into the blood stream. The hormone crosses the blood-brain barrier, binds to a receptor in the hypothalamus, and sends a signal to suppress appetite. The effects of the bone’s emission of LCN2 have also been shown to suppress appetite in both lean and obese mice, a key finding since appetite-regulating drugs typically decline in efficiency over time. Since hormones found in humans and mice share the same functions, it is likely that the effects of LCN2 secretion from the osteoblasts can be applied to humans, and later be used to aid in future weight loss treatments.
Source: Mosialou, I., Shikhel, S., Liu, J., Maurizi, A., Luo, N., He, Z., . . . Kousteni, S. (2017). MC4R-dependent suppression of appetite by bone-derived lipocalin 2. Nature.