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1 Evans Department of Medicine, Boston University Medical Center, Boston, MA, USA
2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
3 Department of Surgery, Boston University Medical Center, Boston, MA, USA
4 AdipoGenix, Inc, Boston, MA, USA
5 Evans Department of Medicine, Boston University Medical Center, Boston, MA, USA; Department of Biochemistry, Boston University Medical Center, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: kirkland{at}bu.edu.
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
-induced apoptosis than omental
preadipocytes. We found higher replicative potential in subcutaneous and mesenteric than
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 than the other. The former was more abundant in subcutaneous and
mesenteric than 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 both subtypes are of preadipocyte lineage. After subcloning 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.
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