ΔFosB Requires Galanin, but not Leptin, to Increase Bone Mass via the Hypothalamus, but both are needed to increase Energy expenditure
Open Access
- 18 April 2019
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 34 (9), 1707-1720
- https://doi.org/10.1002/jbmr.3741
Abstract
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.Keywords
Funding Information
- National Institute on Aging (AG‐040222)
This publication has 73 references indexed in Scilit:
- Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in miceJCI Insight, 2012
- Ablation of neurons expressing agouti-related protein, but not melanin concentrating hormone, in leptin-deficient mice restores metabolic functions and fertilityProceedings of the National Academy of Sciences of the United States of America, 2012
- Leptin Does Not Directly Affect CNS Serotonin Neurons to Influence AppetiteCell Metabolism, 2011
- CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neuronsGenes & Development, 2010
- Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy MetabolismCell, 2010
- Insulin Receptor Signaling in Osteoblasts Regulates Postnatal Bone Acquisition and Body CompositionCell, 2010
- Leptin Functions Peripherally to Regulate Differentiation of Mesenchymal Progenitor CellsThe International Journal of Cell Cloning, 2010
- Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and FertilityCell Metabolism, 2010
- A Serotonin-Dependent Mechanism Explains the Leptin Regulation of Bone Mass, Appetite, and Energy ExpenditureCell, 2009
- Endocrine Regulation of Energy Metabolism by the SkeletonCell, 2007