Obesity is a serious medical problem. Extreme adiposity results from increases in both fat cell size and number. Mature fat cells are terminally differentiated; new adipocytes arise from preadipocytes that are recruited from mesenchymal stem cells (MSCs) present in the vascular stroma of adipose tissue in adults. Differentiation of MSCs to adipocytes is a two-step process - commitment to the adipocyte lineage and differentiation of preadipocytes into mature adipocytes. Although a great deal is known about the mechanisms whereby preadipocytes differentiate into adipocytes, there is a paucity of information regarding the commitment of pluripotent MSCs to the adipocyte lineage. I hypothesize that """"""""commitment genes"""""""" are expressed by committed preadipocytes but not by their pluripotent MSC progenitors. I propose to identify these genes by examining differential gene expression between MSCs and preadipocytes. In addition, mass spectrometry-based approaches will be used to identify changes in the proteome accompanying the MSC to preadipocyte transition. Further, the ability of the identified genes/proteins to induce adipocyte lineage commitment will be tested with both ex vivo and in vivo models. Targets for obesity therapies may be found. ? ?
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