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

Autor: Li Z; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States., Bowers E; University of Michigan Medical School, Department of Pediatrics, Ann Arbor, United States., Zhu J; Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, United States.; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Yu H; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States., Hardij J; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States., Bagchi DP; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States., Mori H; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States., Lewis KT; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States., Granger K; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States., Schill RL; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States., Romanelli SM; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States., Abrishami S; University of Michigan Medical School, Department of Pediatrics, Ann Arbor, United States., Hankenson KD; Department of Orthopedic Surgery, University of Michigan Medical School, Ann Arbor, United States., Singer K; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States.; University of Michigan Medical School, Department of Pediatrics, Ann Arbor, United States., Rosen CJ; Maine Medical Center Research Institute, Scarborough, United States., MacDougald OA; University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, United States.; University of Michigan Medical School, Department of Internal Medicine, Ann Arbor, United States.
Jazyk: angličtina
Zdroj: ELife [Elife] 2022 Jun 22; Vol. 11. Date of Electronic Publication: 2022 Jun 22.
DOI: 10.7554/eLife.78496
Abstrakt: 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, Pnpla2 gene). BMAd- Pnpla2 -/- 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 ad libitum, BMAd lipolysis is necessary to maintain myelopoiesis and bone mass under caloric restriction. BMAd-specific Pnpla2 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.
Competing Interests: ZL, EB, JZ, HY, JH, DB, HM, KL, KG, RS, SR, SA, KH, KS, CR, OM No competing interests declared
(© 2022, Li et al.)
Databáze: MEDLINE