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

Research output: Contribution to journalArticle

168 Scopus citations

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 {alpha}-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 {gamma}2, and CCAAT/enhancer-binding protein {alpha} 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.

Original languageEnglish (US)
Pages (from-to)2571-2578
Number of pages8
JournalDiabetes
Volume55
Issue number9
DOIs
StatePublished - Sep 1 2006

Keywords

  • C/EBP{alpha}
  • CCAAT/enhancer-binding protein {alpha}
  • FBS, fetal bovine serum
  • G3PD, glycerol-3-phosphate dehydrogenase
  • PPAR, peroxisome proliferator-activated receptor
  • hTERT, human telomere reverse transcriptase
  • mRNA, messenger RNA

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Tchkonia, T., Giorgadze, N., Pirtskhalava, T., Thomou, T., DePonte, M., Koo, A., Forse, R. A., Chinnappan, D., Martin-Ruiz, C., Von Zglinicki, T., & Kirkland, J. L. (2006). Fat depot-specific characteristics are retained in strains derived from single human preadipocytes. Diabetes, 55(9), 2571-2578. https://doi.org/10.2337/db06-0540