BIOHW 8 |
| Fat depots vary in size, function, and potential contribution to disease, including metabolic syndrome. Fat tissue turns over throughout life, with preadipocytes undergoing adipogenesis to replace fat cells. Lipid accumulation and adipogenic transcription factor expression varies among differentiated preadipocytes cultured from different depots, suggesting that depot-specific preadipocyte properties contribute to regional variation. We used preadipocytes from different human depots (abdominal subcutaneous, mesenteric, and omental) to determine if inherent properties of fat cell progenitors differ. Genome-wide expression profiles of preadipocytes from different depots were distinct. Genes that regulate early development, including homeotic and lineage genes, were the category that varied most (P<10-30 by GO analysis). These depot-specific profiles were found in males and females, and lean as well as obese subjects. The profiles persisted for 40 population doublings in strains made from single preadipocytes from different depots by expressing telomerase. Visceral fat was not homogeneous: mesenteric preadipocytes had an expression profile closer to that of subcutaneous than omental preadipocytes, the other main visceral depot. Preadipocyte morphology was distinct: observers were able to identify depot origin correctly. Depot specific morphology persisted in the telomerase expressing strains for 40 population doublings, as did differences in preadipocyte replication, subtype abundance, adipogenesis, and susceptibility to apoptosis. Serial arrays of differentiating preadipocytes (20 time points from 15 minutes to 30 days) from the 3 depots indicate that the magnitude rather than timing of changes in gene expression accounts for regional variation in extent of adipogenesis. Human omental preadipocytes transplanted into immunodeficient mice and rats developed into fat that exhibited a greater increase in lipolysis in response to isoproterenol than transplanted subcutaneous preadipocytes, reflecting regional differences in catecholamine-stimulated lipolysis in human fat tissue. Thus, fat cell progenitors from different regions are effectively distinct, consistent with different fat depots being separate mini-organs. |
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Genomics of Obesity
1:30 PM-4:25 PM, Monday, August 20, 2007 BCEC -- 203, Oral
Biotechnology of Health and Wellness |