ΔFosB Requires Galanin, but not Leptin, to Increase Bone Mass via the Hypothalamus, but both are needed to increase Energy expenditure
| Autor: | Glenn C. Rowe, Kenichi Nagano, Roland Baron, Anna Idelevich, Kazusa Sato, Francesca Gori |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Leptin medicine.medical_specialty Anabolism Endocrinology Diabetes and Metabolism Hypothalamus 030209 endocrinology & metabolism Galanin Biology Bone and Bones Article 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Orthopedics and Sports Medicine Mice Knockout Leptin Deficiency digestive oral and skin physiology Body Weight Organ Size Mice Inbred C57BL Enolase 2 030104 developmental biology Endocrinology Glucose Phosphopyruvate Hydratase Energy Metabolism Proto-Oncogene Proteins c-fos Homeostasis hormones hormone substitutes and hormone antagonists Gene Deletion |
| Zdroj: | J Bone Miner Res |
| ISSN: | 1523-4681 |
| Popis: | Energy metabolism and bone homeostasis share several regulatory pathways. The AP1 transcription factor ΔFosB and leptin both regulate energy metabolism and bone, yet whether their pathways intersect is not known. Transgenic mice overexpressing ΔFosB 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 ΔFosB 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 ΔFosB in the VHT. To address this question, we used adeno-associated virus (AAV) expression of ΔFosB in the VHT of leptin-deficient ob/ob mice and genetic crossing of ENO2-ΔFosB with ob/ob mice. In both models, leptin deficiency prevented ΔFosB-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 ΔFosB-triggered increase in bone mass. Unlike leptin deficiency, galanin deficiency blocked both the metabolic and the bone ΔFosB-induced effects. Overall, our data demonstrate that, while the catabolic energy metabolism effects of ΔFosB require intact leptin and galanin signaling, the bone mass-accruing effects of ΔFosB require galanin but are independent of leptin. © 2019 American Society for Bone and Mineral Research. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text