Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits
Ziru Li, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Emily Bowers, Department of Pediatrics, University of Michigan-Ann Arbor, Ann Arbor, United States.
Junxiong Zhu, Department of Orthopedic Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States.
Hui Yu, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Julie Hardij, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Devika P. Bagchi, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Hiroyuki Mori, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Kenneth T. Lewis, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Katrina Granger, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Rebecca L. Schill, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Steven M. Romanelli, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Simin Abrishami, Department of Pediatrics, University of Michigan-Ann Arbor, Ann Arbor, United States.
Kurt D. Hankenson, Department of Orthopedic Surgery, University of Michigan-Ann Arbor, Ann Arbor, United States.
Kanakadurga Singer, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Clifford J. Rosen, Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, United States.
Ormond MacDougald, Department of Molecular and Integrative Physiology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Abstract
To investigate roles for bone marrow adipocyte (BMAd) lipolysis in bone homeostasis, we created a BMAd-specific Cre mouse model in which we knocked out adipose triglyceride lipase (ATGL, gene). BMAd- mice have impaired BMAd lipolysis, and increased size and number of BMAds at baseline. Although energy from BMAd lipid stores is largely dispensable when mice are fed , BMAd lipolysis is necessary to maintain myelopoiesis and bone mass under caloric restriction. BMAd-specific deficiency compounds the effects of caloric restriction on loss of trabecular bone in male mice, likely due to impaired osteoblast expression of collagen genes and reduced osteoid synthesis. RNA sequencing analysis of bone marrow adipose tissue reveals that caloric restriction induces dramatic elevations in extracellular matrix organization and skeletal development genes, and energy from BMAd is required for these adaptations. BMAd-derived energy supply is also required for bone regeneration upon injury, and maintenance of bone mass with cold exposure.
