Tchkonia Tamara, Giorgadze Nino, Pirtskhalava Tamar, Thomou Thomas, DePonte Matthew, Koo Ada, Forse R Armour, Chinnappan Dharmaraj, Martin-Ruiz Carmen, von Zglinicki Thomas, Kirkland James L
Department of Medicine, Boston University, Boston, MA 02118, USA.
Diabetes. 2006 Sep;55(9):2571-8. doi: 10.2337/db06-0540.
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.
脂肪储存库在大小、功能以及对疾病的潜在影响方面存在差异。由于脂肪组织在整个生命过程中都会更新，前脂肪细胞的特性可能导致这种区域差异。为了探究来自不同储存库的前脂肪细胞是否存在差异，我们通过稳定表达人端粒逆转录酶（hTERT），从单个腹部皮下、肠系膜和网膜的人前脂肪细胞中生成了前脂肪细胞系。这些细胞系可以反复传代培养，并保留分化能力，而原代前脂肪细胞的脂肪生成和复制能力会随着传代培养而下降。原代网膜前脂肪细胞的端粒最长，其复制速度比肠系膜或腹部皮下前脂肪细胞慢。即使经过40次群体倍增，皮下hTERT表达细胞系的复制能力、快速复制的前脂肪细胞亚型的丰度以及对肿瘤坏死因子α诱导的凋亡的抗性最高，肠系膜的次之，网膜hTERT表达细胞系的最低，这与原代前脂肪细胞的情况相同。与原代前脂肪细胞一样，皮下hTERT表达细胞系比网膜细胞积累了更多脂质，并且表达了更多的脂肪细胞脂肪酸结合蛋白（aP2）、过氧化物酶体增殖物激活受体γ2和CCAAT/增强子结合蛋白α，而hTERT的丰度相似。因此，尽管经过了40次群体倍增，源自单个前脂肪细胞的hTERT细胞系仍保留了脂肪储存库特异性的细胞动态特征，这与导致脂肪组织功能区域差异的遗传过程一致。
