Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits

Document Type

Article

Publication Date

6-22-2022

Institution/Department

Maine Medical Center Research Institute

Journal Title

eLife

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.

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