A bone-specific adipogenesis pathway in fat-free mice defines key origins and adaptations of bone marrow adipocytes with age and disease

Elife. 2021 Aug 11:10:e66275. doi: 10.7554/eLife.66275.

Abstract

Bone marrow adipocytes accumulate with age and in diverse disease states. However, their origins and adaptations in these conditions remain unclear, impairing our understanding of their context-specific endocrine functions and relationship with surrounding tissues. In this study, by analyzing bone and adipose tissues in the lipodystrophic 'fat-free' mouse, we define a novel, secondary adipogenesis pathway that relies on the recruitment of adiponectin-negative stromal progenitors. This pathway is unique to the bone marrow and is activated with age and in states of metabolic stress in the fat-free mouse model, resulting in the expansion of bone marrow adipocytes specialized for lipid storage with compromised lipid mobilization and cytokine expression within regions traditionally devoted to hematopoiesis. This finding further distinguishes bone marrow from peripheral adipocytes and contributes to our understanding of bone marrow adipocyte origins, adaptations, and relationships with surrounding tissues with age and disease.

Keywords: adipogenesis; adiponectin; aging; bone marrow adipocyte; cell biology; metabolism; mouse; progenitor cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / physiology*
  • Adipogenesis / physiology*
  • Adipose Tissue / metabolism
  • Adipose Tissue / physiology
  • Age Factors
  • Animals
  • Bone Marrow / metabolism
  • Bone Marrow / physiology*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / physiology
  • Bone and Bones / metabolism
  • Bone and Bones / physiology
  • Cell Differentiation
  • Female
  • Hematopoiesis / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Osteoblasts / metabolism
  • Osteoblasts / physiology