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

被引:109
作者
Majka, Susan M. [1 ,5 ,6 ]
Fox, Keith E. [5 ,6 ]
Psilas, John C. [5 ,6 ]
Helm, Karen M. [2 ]
Childs, Christine R. [2 ]
Acosta, Alistaire S. [2 ]
Janssen, Rachel C. [4 ]
Friedman, Jacob E. [4 ]
Woessner, Brian T. [3 ]
Shade, Theodore R. [3 ]
Varella-Garcia, Marileila
Klemm, Dwight J. [1 ,5 ,6 ]
机构
[1] Univ Colorado, Charles C Gates Regenerat Med & Stem Cell Biol Pr, Aurora, CO 80045 USA
[2] Univ Colorado, Canc Ctr Flow Cytometry Core, Aurora, CO 80045 USA
[3] Univ Colorado, Microarray Core Labs, Aurora, CO 80045 USA
[4] Univ Colorado, Metab Core Serv Ctr, Dept Pediat, Aurora, CO 80045 USA
[5] Univ Colorado, Cardiovasc Pulm Res Lab, Aurora, CO 80045 USA
[6] Univ Colorado, Dept Med, Aurora, CO 80045 USA
基金
美国国家卫生研究院;
关键词
bone marrow; hematopoietic; stem cell; PPAR-GAMMA ACTIVATION; HEMATOPOIETIC STEM; INSULIN-RESISTANCE; CELLS; EXPRESSION; DIFFERENTIATION; PROTEIN; MACROPHAGES; OBESITY; TISSUE;
D O I
10.1073/pnas.1003512107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:14781 / 14786
页数:6
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