How Hunger Neurons Control Bone Mass

In an advance that helps clarify the role of a cluster of neurons in the brain, Yale School of Medicine researchers have found that these neurons not only control hunger and appetite, but also regulate bone mass. According to one of the senior authors, Tamas L. Horvath, director of the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism:

“We have found that the level of your hunger could determine your bone structure. The less hungry you are, the lower your bone density, and surprisingly, the effects of these neurons on bone mass are independent of the effect of the hormone leptin on these same cells.”

Horvath and his team focused on agouti-related peptide (AgRP) neurons in the hypothalamus, which control feeding and compulsive behaviors.

Using mice that were genetically-engineered so their cells selectively interfere with the AgRP neurons, the team found that these same cells are also involved in determining bone mass.

neurons
The team further found that when the AgRP circuits were impaired, this resulted in bone loss and osteopenia in mice — the equivalent of osteoporosis in women. But when the team enhanced AgRP neuronal activity in mice, this actually promoted increased bone mass.

Co-senior author Karl Insogna, M.D., professor of medicine, and director of the Yale Bone Center, said:

“Taken together, these observations establish a significant regulatory role for AgRP neurons in skeletal bone metabolism independent of leptin’s action. Based on our findings, it seems that the effect of AgRP neurons on bone metabolism in adults is mediated at least in part by the sympathetic nervous system, but more than one pathway is likely involved.

There are other mechanisms by which the AgRP system can affect bone mass, including actions on the thyroid, adrenal and gonad systems. Further studies are needed to assess the hormonal control of bone metabolism as a pathway modulated by AgRP neurons.”

Jae Geun Kim, Ben-Hua Sun, Marcelo O. Dietrich, Marco Koch, Gang-Qing Yao, and Sabrina Diano
AgRP Neurons Regulate Bone Mass
Cell Reports, September 2015 DOI: 10.1016/j.celrep.2015.08.070

Top Image: Paul R. Odgren, Ph.D., University of Massachusetts Medical School. Image of cartilage (purple and white) from a young mouse femur, osteoclasts (red) surrounding a blood vessel filled with red blood cells (yellow).