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We often think of bones as immobile structures, but scientists are learning that bones are far more dynamic than once believed. Research has shown that they play important roles in immunity, kidney health, and metabolism. In a recent study, Dr. Stavroula Kousteni, Associate Professor at Columbia University Medical Center, led her team to the discovery that lipocalin 2, a hormone secreted by bone cells, suppresses appetite in mice. The study findings will potentially add to the understanding of weight management and maintaining a healthy metabolism and also raise questions about the possibility of other bone-derived hormones and what their potential functions could be.

Previously, it was thought that lipocalin 2 was only secreted by adipose tissue and contributed to obesity. Using genetically modified mice, Dr. Kousteni and her team showed lipocalin 2 levels were tenfold higher in osteoblasts (the bone forming cells) versus fat.  In mice that were engineered to lack lipocalin 2 in fat cells or osteoblasts, the investigators found that only mice lacking lipocalin 2 in the osteoblasts had increased food intake, body weight, and impaired glucose metabolism. In normal mice and in obese leptin-receptor deficient mice, administration of lipocalin 2 suppressed appetite, decreased body weight and improved glucose metabolism.

The brain controls feeding behavior. The Kousteni team demonstrated that lipocalin 2 crosses the blood-brain barrier and binds to the melanocortin 4 receptor, (which is linked to feeding behavior) in the neurons of the hypothalamus, thereby activating appetite-suppressing pathways in the brain. This shows at least in mice, that control of appetite is, in part, an endocrine function of the bone. The study findings could lead to the development of new treatments for obesity, type 2 diabetes, and other metabolic disorders. Interestingly, type ll diabetic patients with higher lipocalin 2 levels had lower body weight and glycated hemoglobin levels, the latter being a measure of glucose control.

“In recent years, studies at CUMC and elsewhere have shown that bone is an endocrine organ and produces hormones that affect brain development, glucose balance, kidney function, and male fertility,” says Dr. Kousteni. “Our findings add a critical new function of bone hormones to this list—appetite suppression—which may open a wholly new approach to the treatment of metabolic disorders.”¹

 

¹ “Bone-Derived Hormone Suppresses Appetite in Mice.” Columbia University Medical Center Newsroom. Columbia University Medical Center, 08 Mar. 2017. Web.