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Am J Physiol Endocrinol Metab (September 19, 2006). doi:10.1152/ajpendo.00202.2006
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Submitted on April 26, 2006
Accepted on September 6, 2006

Identification of Depot-Specific Human Fat Cell Progenitors through Distinct Expression Profiles and Developmental Gene Patterns

Tamara Tchkonia1, Marc Lenburg2, Thomas Thomou1, Nino Giorgadze1, Garrett Frampton2, Tamar Pirtskhalava1, Andrew Cartwright1, Mark Cartwright1, John Flanagan1, Iordanes Karagiannides3, Norman Gerry2, R Armour Forse4, Yourka Tchoukalova5, Michael D. Jensen6, Charalabos Pothoulakis3, and James L. Kirkland7*

1 Medicine, Boston University, Boston, Massachusetts, United States
2 Genetics and Genomics, Boston University, Boston, Massachusetts, United States
3 Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
4 Surgery, Creighton University, Omaha, Nebraska, United States
5 Endocrine Research Unit, Mayo Clinic Foundation, Rochester, Minnesota, United States
6 Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, United States
7 Medicine, Boston University Medical Center, Boston, Massachusetts, United States

* To whom correspondence should be addressed. E-mail: kirkland{at}bu.edu.

Anatomically separate fat depots differ in size, function, and contribution to pathological states such as the metabolic syndrome. We isolated preadipocytes from different human fat depots to determine if the basis for this variation is partly attributable to differences in inherent properties of fat cell progenitors. We found that genome-wide expression profiles of primary preadipocytes cultured in parallel from abdominal subcutaneous, mesenteric, and omental fat depots were distinct. Interestingly, visceral fat was not homogeneous. Preadipocytes from one of the two main visceral depots, mesenteric fat, had an expression profile closer to that of subcutaneous than omental preadipocytes, the other main visceral depot. Expression of genes that regulate early development, including homeotic genes, differed extensively among undifferentiated preadipocytes isolated from different fat depots. These profiles were confirmed by real time PCR analysis of preadipocytes from additional lean and obese, male and female subjects. We made preadipocyte strains from single abdominal subcutaneous and omental preadipocytes by expressing telomerase. Depot-specific developmental gene expression profiles persisted for 40 population doublings in these strains. Thus, human fat cell progenitors from different regions are effectively distinct, consistent with different fat depots being separate mini-organs.




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