Hormone secreted by bones influences the appetite

A hormone found to suppress appetite after meals in mice could one day have weight-loss applications in humans.

Bone was recently found to be part of the endocrine system, which means it releases hormones into the blood. Now, a new study in Nature has found that Lipocalin 2 (LCN2) is among the hormones that bone secretes. The hormone can suppress appetite in mice, revealing a previously unknown type of appetite regulation that has possible weight loss applications.

We spoke with study author Stavroula Kousteni of Columbia University about the work.

ResearchGate: What was the motivation behind this study?

Stavroula Kousteni: Our interest was to examine whether bone, acting as an endocrine organ, could secrete hormones to regulate energy homeostasis, perhaps by regulating additional and yet unknown metabolic functions. Studies from our laboratory supported this notion, because they 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.

RG: What did you find?

Kousteni: We found that Lipocalin 2 is released into the blood by osteoblasts, crosses the blood-brain barrier, binds to a receptor in the brain’s hypothalamus, and activates a signaling pathway that suppresses appetite.

After a meal, Lipocalin 2 levels in the serum of mice rapidly increase, and this increase is required for suppression of appetite after eating.

RG: Can you tell us about the significance of these results?

Kousteni: The finding broadens our understanding of how appetite is controlled and provides another tool for potentially translating these findings into the clinic.

Since the underlying mechanisms that regulate appetite—and the abnormal glucose metabolism and obesity associated with metabolic disease—are not fully understood, the skeleton may provide new insights into the pathogenesis of these diseases.

RG: Do you think bone plays a similar role for humans?

Kousteni: I think that it most likely does. All hormones that have a function in rodents also have the same function in humans. For Lipocalin 2, we show that serum levels inversely correlate with body weight and the long-term blood sugar marker HbA1c in type 2 diabetes mellitus patients. Also, there is evidence in the literature that Lipocalin 2 serum levels increase in lean humans after a meal, just as we observed in mice. All these observations are indication of a similar type of regulation and function in humans.

RG: What applications could your findings have?

Kousteni: One of the key findings of this work was that exogenous Lipocalin 2 can supress appetite chronically in both lean and obese mice. This property, if reproduced in humans, can potentially find an application in weight loss treatment, since current appetite-regulating medications lose their suppressive effect with time.

RG: What’s next for your research?

Kousteni: We plan to generate a comprehensive picture of how bone regulates energy metabolism using Lipocalin 2. This approach will also reveal new signaling pathways and molecular targets that may find applications in the field of diabetes management. We would also like to understand the mechanism through which bone regulates Lipocalin 2 expression, and examine whether the pattern of regulation is conserved in humans.

Featured image of Osteoblasts courtesy of Wikipedia.