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Obesity Studies

Fat Depot–Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes

  1. Tamara Tchkonia1,
  2. Nino Giorgadze1,
  3. Tamar Pirtskhalava1,
  4. Thomas Thomou1,
  5. Matthew DePonte2,
  6. Ada Koo2,
  7. R. Armour Forse3,
  8. Dharmaraj Chinnappan1,
  9. Carmen Martin-Ruiz4,
  10. Thomas von Zglinicki4 and
  11. James L. Kirkland1,5
  1. 1Department of Medicine, Boston University, Boston, Massachusetts
  2. 2AdipoGenix, Boston, Massachusetts
  3. 3Department of Surgery, Creighton University, Omaha, Nebraska
  4. 4Henry Wellcome Biogerontology Laboratory, Institute for Ageing and Health, University of Newcastle, Newcastle, U.K
  5. 5Department of Biochemistry, Boston University, Boston, Massachusetts
  1. Address correspondence and reprint requests to James L. Kirkland, MD, PhD, Boston University, 88 East Newton St., Robinson 2, Boston, MA 02118. E-mail: kirkland{at}bu.edu
Diabetes 2006 Sep; 55(9): 2571-2578. https://doi.org/10.2337/db06-0540
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Abstract

Fat depots vary in size, function, and potential contribution to disease. Since fat tissue turns over throughout life, preadipocyte characteristics could contribute to this regional variation. To address whether preadipocytes from different depots are distinct, we produced preadipocyte strains from single abdominal subcutaneous, mesenteric, and omental human preadipocytes by stably expressing human telomere reverse transcriptase (hTERT). These strains could be subcultured repeatedly and retained capacity for differentiation, while primary preadipocyte adipogenesis and replication declined with subculturing. Primary omental preadipocytes, in which telomeres were longest, replicated more slowly than mesenteric or abdominal subcutaneous preadipocytes. Even after 40 population doublings, replication, abundance of the rapidly replicating preadipocyte subtype, and resistance to tumor necrosis factor α–induced apoptosis were highest in subcutaneous, intermediate in mesenteric, and lowest in omental hTERT-expressing strains, as in primary preadipocytes. Subcutaneous hTERT-expressing strains accumulated more lipid and expressed more adipocyte fatty acid–binding protein (aP2), peroxisome proliferator–activated receptor γ2, and CCAAT/enhancer-binding protein α than omental cells, as in primary preadipocytes, while hTERT abundance was similar. Thus, despite dividing 40 population doublings, hTERT strains derived from single preadipocytes retained fat depot–specific cell dynamic characteristics, consistent with heritable processes contributing to regional variation in fat tissue function.

  • C/EBPα, CCAAT/enhancer-binding protein α
  • FBS, fetal bovine serum
  • G3PD, glycerol-3-phosphate dehydrogenase
  • hTERT, human telomere reverse transcriptase
  • mRNA, messenger RNA
  • PPAR, peroxisome proliferator–activated receptor
  • TNF, tumor necrosis factor
  • Received April 20, 2006.
  • Accepted June 8, 2006.
  • DIABETES
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Fat Depot–Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes
Tamara Tchkonia, Nino Giorgadze, Tamar Pirtskhalava, Thomas Thomou, Matthew DePonte, Ada Koo, R. Armour Forse, Dharmaraj Chinnappan, Carmen Martin-Ruiz, Thomas von Zglinicki, James L. Kirkland
Diabetes Sep 2006, 55 (9) 2571-2578; DOI: 10.2337/db06-0540

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Fat Depot–Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes
Tamara Tchkonia, Nino Giorgadze, Tamar Pirtskhalava, Thomas Thomou, Matthew DePonte, Ada Koo, R. Armour Forse, Dharmaraj Chinnappan, Carmen Martin-Ruiz, Thomas von Zglinicki, James L. Kirkland
Diabetes Sep 2006, 55 (9) 2571-2578; DOI: 10.2337/db06-0540
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Keywords

C/EBPα, CCAAT/enhancer-binding protein α
FBS, fetal bovine serum
G3PD, glycerol-3-phosphate dehydrogenase
hTERT, human telomere reverse transcriptase
mRNA, messenger RNA
PPAR, peroxisome proliferator–activated receptor
TNF, tumor necrosis factor

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