title: Fat depot-specific characteristics are retained in strains derived from single human preadipocytes.
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 gamma2, 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.
authors.affiliation: Department of Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Tchkonia
authors.forename: Nino
authors.initials: N
authors.lastname: Giorgadze
authors.forename: Tamar
authors.initials: T
authors.lastname: Pirtskhalava
authors.forename: Thomas
authors.initials: T
authors.lastname: Thomou
authors.forename: Matthew
authors.initials: M
authors.lastname: DePonte
authors.forename: Ada
authors.initials: A
authors.lastname: Koo
authors.forename: R Armour
authors.initials: RA
authors.lastname: Forse
authors.forename: Dharmaraj
authors.initials: D
authors.lastname: Chinnappan
authors.forename: Carmen
authors.initials: C
authors.lastname: Martin-Ruiz
authors.forename: Thomas
authors.initials: T
authors.lastname: von Zglinicki
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
mesh_terms: D050153:Abdominal Fat / Q000166:cytology; D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000166:cytology; D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008643:Mesentery / Q000166:cytology; D008875:Middle Aged; D009852:Omentum / Q000166:cytology; D013234:Stem Cells / Q000166:cytology; D050151:Subcutaneous Fat / Q000166:cytology; D019098:Telomerase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D004268:DNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D019098:Telomerase