De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific

Abstract

It is generally assumed that white adipocytes arise from resident adipose tissue mesenchymal progenitor cells. We challenge this paradigm by defining a hematopoietic origin for both the de novo development of a subset of white adipocytes in adults and a previously uncharacterized adipose tissue resident mesenchymal progenitor population. Lineage and cytogenetic analysis revealed that bone marrow progenitor (BMP)-derived adipocytes and adipocyte progenitors arise from hematopoietic cells via the myeloid lineage in the absence of cell fusion. Global gene expression analysis indicated that the BMP-derived fat cells are bona fide adipocytes but differ from conventional white or brown adipocytes in decreased expression of genes involved in mitochondrial biogenesis and lipid oxidation, and increased inflammatory gene expression. The BMP-derived adipocytes accumulate with age, occur in higher numbers in visceral than in subcutaneous fat, and in female versus male mice. BMP-derived adipocytes may, therefore, account in part for adipose depot heterogeneity and detrimental changes in adipose metabolism and inflammation with aging and adiposity.

Characterization of Human Adipose Tissue-Resident Hematopoietic Cell Populations Reveals a Novel Macrophage Subpopulation with CD34 Expression and Mesenchymal Multipotency

“…This suggests that both ASCs and macrophages have substantial plasticity and are closely related to each other. In addition, some studies suggest that certain adipocytes and adipose progenitor cells originate from bone marrow-derived cells [44][45][46], although there was a contradictory report that failed to demonstrate transdifferentiation of bone marrow-derived cells into adipocytes [47]. Our study demonstrated high adipogenic differentiation capacity of CD34 + /CD206…”

Concise Review: Adipose-Derived Stromal Vascular Fraction Cells and Stem Cells: Let's Not Get Lost in Translation

“…For example, a recent murine study found that a subpopulation of adipocyte progenitor cells are most frequent in visceral as opposed to subcutaneous adipose depots, increase with advancing age, and are more frequently observed in female donors [8]. A limited number of human studies provide similar findings.…”

Adipogenesis

“…As reviewed in Figure 2, these results suggest that brown cells in BAT and brown fat-like cells in WAT have different cellular origins, and the transcriptional modulator PRDM16 plays an important role in both of these cell types to regulate genes required for thermogenesis (Seale et al 2011). To make the situation more complex, there is also evidence to indicate that bone marrow progenitor-derived adipocytes and adipocyte progenitors can arise from hematopoietic cells via the myeloid lineage (Majka et al 2010). Collectively, these recent studies suggest that our understanding of the origin of adipocytes is rapidly changing, and additional studies will be necessary to clarify our understanding of this emerging area of biology.…”