"Mediation of the acute stress response by the skeleton," Cell Metabolism (2019). DOI: 10.1016/j.cmet.2019.08.012 , https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30441-3 Mediation of the Acute Stress Response by the Skeleton Author links open overlay panelJulian MeyerBerger12GerardKarsenty19 https://doi.org/10.1016/j.cmet.2019.08.012Get rights and content Highlights • The ASR stimulates osteocalcin release from bone within minutes • Glutamate uptake into osteoblasts is required for osteocalcin release during an ASR • Osteocalcin inhibits the parasympathetic tone during an ASR • In adrenal insufficiency, increased osteocalcin levels enable an ASR to occur Summary We hypothesized that bone evolved, in part, to enhance the ability of bony vertebrates to escape danger in the wild. In support of this notion, we show here that a bone-derived signal is necessary to develop an acute stress response (ASR). Indeed, exposure to various types of stressors in mice, rats (rodents), and humans leads to a rapid and selective surge of circulating bioactive osteocalcin because stressors favor the uptake by osteoblasts of glutamate, which prevents inactivation of osteocalcin prior to its secretion. Osteocalcin permits manifestations of the ASR to unfold by signaling in post-synaptic parasympathetic neurons to inhibit their activity, thereby leaving the sympathetic tone unopposed. Like wild-type animals, adrenalectomized rodents and adrenal-insufficient patients can develop an ASR, and genetic studies suggest that this is due to their high circulating osteocalcin levels. We propose that osteocalcin defines a bony-vertebrate-specific endocrine mediation of the ASR. Bone, not adrenaline, drives fight or flight response September 12, 2019 , Columbia University Irving Medical Center https://m.phys.org/news/2019-09-bone-adrenaline-flight-response.html But a new study from Columbia researchers suggests that bony vertebrates can't muster this response to danger without the skeleton. The researchers found in mice and humans that almost immediately after the brain recognizes danger, it instructs the skeleton to flood the bloodstream with the bone-derived hormone osteocalcin, which is needed to turn on the fight or flight response. .... A series of studies since then have shown that osteocalcin helps regulate metabolism by increasing the ability of cells to take in glucose, improves memory, and helps animals run faster with greater endurance.