Patrick Laharrague and Louis Casteilla

Abstract

Bone marrow (BM) adipose tissue should no longer be considered simply as a filling material for bone cavities that is not needed for hematopoietic activity. In addition to its potential role as an energy store, BM adipose tissue exhibits a considerable adaptive plasticity and secretes a broad spectrum of hormones, cytokines and growth factors whose receptors are present on different cells of the stromal microenvironment. BM adipocytes, originating like osteoblasts from mesenchymal stem cells, display a marked metabolic and secretory activity. Among the various secreted adipokines, leptin, and adiponectin have opposite effects on hematopoiesis, immunity, inflammation, and bone remodeling. As a whole, a counterbalance exists between adipogenesis and erythropoiesis, and between adipose and bone formation. The better knowledge of the different paracrine and endocrine agents involved in the subtle and complex regulation of hematopoiesis and its osseous environment suggests that BM adipose tissue may represent a target for drugs in situations such as blood diseases or osteoporosis.

Key Words: Bone marrow; adipocytes; microenvironment; mesenchymal stem cells; hematopoiesis; osteogenesis; adipogenesis.

Many studies have focused on brown and white fat in both rodents and humans. The organization and properties of bone marrow (BM) adipose tissue have received much less attention.

Although adipocytes are the most abundant cell type found in adult human bone marrow, their function is not fully understood. Several hypotheses—often conflicting— have been proposed to clarify their role. Most of them have not been rigorously verified (1). For some authors, marrow fat simply fills the spaces free of hematopoietic cells in the closed and rigid cavity of bone, accommodating to hematopoietic demands by altering its volume—i.e., by contracting in the case of heightened hematopoiesis or by expanding in the event of decreased marrow activity (2,3). Evans et al. considered marrow adipose tissue as an ordinary fat pad, the free fatty acids produced by lipolysis raising the circulation to participate in the general metabolism of the organism (4). Others have suggested that the BM fat stores are important for local nutrition rather than for total energy supplies (5). However, most recent studies indicate that BM adipose tissue possesses a significant endocrine function, considerable adaptive plasticity, and an

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