| First Author | Idelevich A | Year | 2019 |
| Journal | J Bone Miner Res | Volume | 34 |
| Issue | 9 | Pages | 1707-1720 |
| PubMed ID | 30998833 | Mgi Jnum | J:296504 |
| Mgi Id | MGI:6467878 | Doi | 10.1002/jbmr.3741 |
| Citation | Idelevich A, et al. (2019) DeltaFosB Requires Galanin, but not Leptin, to Increase Bone Mass via the Hypothalamus, but both are needed to increase Energy expenditure. J Bone Miner Res 34(9):1707-1720 |
| abstractText | Energy metabolism and bone homeostasis share several regulatory pathways. The AP1 transcription factor DeltaFosB and leptin both regulate energy metabolism and bone, yet whether their pathways intersect is not known. Transgenic mice overexpressing DeltaFosB under the control of the Enolase 2 (ENO2) promoter exhibit high bone mass, high energy expenditure, low fat mass, and low circulating leptin levels. Because leptin is a regulator of bone and DeltaFosB acts on leptin-responsive ventral hypothalamic (VHT) neurons to induce bone anabolism, we hypothesized that regulation of leptin may contribute to the central actions of DeltaFosB in the VHT. To address this question, we used adeno-associated virus (AAV) expression of DeltaFosB in the VHT of leptin-deficient ob/ob mice and genetic crossing of ENO2-DeltaFosB with ob/ob mice. In both models, leptin deficiency prevented DeltaFosB-triggered reduction in body weight, increase in energy expenditure, increase in glucose utilization, and reduction in pancreatic islet size. In contrast, leptin deficiency failed to prevent DeltaFosB-triggered increase in bone mass. Unlike leptin deficiency, galanin deficiency blocked both the metabolic and the bone DeltaFosB-induced effects. Overall, our data demonstrate that, while the catabolic energy metabolism effects of DeltaFosB require intact leptin and galanin signaling, the bone mass-accruing effects of DeltaFosB require galanin but are independent of leptin. (c) 2019 American Society for Bone and Mineral Research. |
