@article{896a68dbfb52417ea9383849e2abbc6a,
title = "Leptin Receptor Promotes Adipogenesis and Reduces Osteogenesis by Regulating Mesenchymal Stromal Cells in Adult Bone Marrow",
abstract = "Summary Skeletal stem cells (SSCs) that are the major source of osteoblasts and adipocytes in adult bone marrow express leptin receptor (LepR). To test whether LepR regulates SSC function, we conditionally deleted Lepr from limb bone marrow stromal cells, but not from the axial skeleton or hypothalamic neurons, using Prx1-Cre. Prx1-Cre;Leprfl/fl mice exhibited normal body mass and normal hematopoiesis. However, limb bones from Prx1-Cre;Leprfl/fl mice exhibited increased osteogenesis, decreased adipogenesis, and accelerated fracture healing. Leptin increased adipogenesis and reduced osteogenesis by activating Jak2/Stat3 signaling in bone marrow stromal cells. A high-fat diet increased adipogenesis and reduced osteogenesis in limb bones from wild-type mice, but not from Prx1-Cre;Leprfl/fl mice. This reflected local effects of LepR on osteogenesis and adipogenesis by bone marrow stromal cells and systemic effects on bone resorption. Leptin/LepR signaling regulates adipogenesis and osteogenesis by mesenchymal stromal cells in the bone marrow in response to diet and adiposity.",
author = "Rui Yue and Zhou, {Bo O.} and Shimada, {Issei S.} and Zhiyu Zhao and Morrison, {Sean J.}",
note = "Funding Information: S.J.M. is a Howard Hughes Medical Institute (HHMI) Investigator, the Mary McDermott Cook Chair in Pediatric Genetics, the director of the Hamon Laboratory for Stem Cells and Cancer, and a Cancer Prevention and Research Institute of Texas Scholar. R.Y. was supported by a Damon Runyon Cancer Research Foundation fellowship. B.O.Z. was supported by a Leukemia and Lymphoma Society fellowship. I.S.S. was supported by an American Heart Association fellowship. We thank Nicolas Loof and the Moody Foundation Flow Cytometry Facility, Kristen Correll for mouse colony management, Jen-Chieh Chuang for assistance with metabolic analysis, Ying Liu and Jerry Q. Feng at the Texas A&M University Baylor College of Dentistry for assistance with microCT analyses, and the UT Southwestern BioHPC (high-performance computing) cluster. We thank Joel Elmquist for advice and thoughtful comments on the manuscript. This work was supported by the Cancer Prevention and Research Institute of Texas. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = jun,
day = "2",
doi = "10.1016/j.stem.2016.02.015",
language = "English (US)",
volume = "18",
pages = "782--796",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "6",
}