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Am J Physiol Endocrinol Metab 288: E267-E277, 2005. First published September 21, 2004; doi:10.1152/ajpendo.00265.2004
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TRANSLATIONAL PHYSIOLOGY

Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots

Tamara Tchkonia,1,* Yourka D. Tchoukalova,5,* Nino Giorgadze,1 Tamar Pirtskhalava,1 Iordanes Karagiannides,1 R. Armour Forse,2 Ada Koo,4 Michael Stevenson,4 Dharmaraj Chinnappan,1 Andrew Cartwright,1 Michael D. Jensen,5 and James L. Kirkland1,3

1Evans Department of Medicine and Departments of 2Surgery and 3Biochemistry, Boston University Medical Center; 4AdipoGenix Inc., Boston, Massachusetts; and 5Division of Endocrinology and Metabolism, Department of Internal Medicine, The Mayo Clinic, Rochester, Minnesota

Submitted 22 June 2004 ; accepted in final form 14 September 2004

Fat depots vary in function and size. The preadipocytes that fat cells develop from exhibit distinct regional characteristics that persist in culture. Human abdominal subcutaneous cultured preadipocytes undergo more extensive lipid accumulation, higher adipogenic transcription factor expression, and less TNF-{alpha}-induced apoptosis than omental preadipocytes. We found higher replicative potential in subcutaneous and mesenteric than in omental preadipocytes. In studies of colonies arising from single preadipocytes, two preadipocyte subtypes were found, one capable of more extensive replication, differentiation, and adipogenic transcription factor expression and less apoptosis in response to TNF-{alpha} than the other. The former was more abundant in subcutaneous and mesenteric than in omental preadipocyte populations, potentially contributing to regional variation in replication, differentiation, and apoptosis. Both subtypes were found in strains derived from single human preadipocytes stably expressing telomerase, confirming that both subtypes are of preadipocyte lineage. After subcloning of cells of either subtype, both subtypes were found, indicating that switching can occur between subtypes. Thus proportions of preadipocyte subtypes with distinct cell-dynamic properties vary among depots, potentially permitting tissue plasticity through subtype selection during development. Furthermore, mesenteric preadipocyte cell-dynamic characteristics are distinct from omental cells, indicating that visceral fat depots are not functionally uniform.

CCAAT/enhancer-binding protein-{alpha}


Address for reprint requests and other correspondence: J. L. Kirkland, Rm. EBRC816, Boston Univ. Medical Center, 88 East Newton St., Boston, MA 02118 (E-mail: kirkland{at}bu.edu)




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