Altered expression of C/EBP family members results in decreased adipogenesis with aging
Altered expression of C/EBP family members results in decreased adipogenesis with aging
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DOI：
10.1152/ajpregu.2001.280.6.r1772
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发表时间：
2001-06-01
影响因子：
2.8
通讯作者：
Kirkland, JL
中科院分区：
文献类型：
--
作者：
Karagiannides, I;Tchkonia, T;Kirkland, JL
脂肪质量、脂肪细胞大小和代谢反应性以及前脂肪细胞分化在中年和老年之间下降。我们发现，CCAAT/增强子结合蛋白（C/EBP）-α的表达，脂肪形成和脂肪细胞功能的关键调节剂，在不同年龄的大鼠在相同条件下培养的分化前脂肪细胞中，随着年龄的增长而显著下降。老年大鼠培养的前脂肪细胞中C/EBP α的过表达恢复了分化为脂肪细胞的能力，表明下游分化依赖性基因保持对脂肪形成调节因子的反应性。C/EBP α表达也随着年龄的增长而减少，在三个不同的仓库和分离的脂肪细胞的脂肪组织。调节C/EBP α表达的C/EBP β的总体水平不随年龄变化，但在培养的前脂肪细胞和分离的脂肪细胞中，截短的显性阴性C/EBP β-肝抑制蛋白（LIP）同种型增加。C/EBP β-LIP在年轻大鼠前脂肪细胞中的过表达损害脂肪形成。C/EBP δ与全长C/EBP β一起作用以增强脂肪形成，随着年龄的增长而下降。因此，涉及C/EBP家族成员变化的脂肪细胞内在过程导致脂肪生成受损和脂肪组织功能随衰老而改变。这些影响可能是可逆的。
Fat mass, adipocyte size and metabolic responsiveness, and preadipocyte differentiation decrease between middle and old age. We show that expression of CCAAT/enhancer binding protein (C/EBP)-alpha, a key regulator of adipogenesis and fat cell function, declined substantially with aging in differentiating preadipocytes cultured under identical conditions from rats of various ages. Overexpression of C/EBP alpha in preadipocytes cultured from old rats restored capacity to differentiate into fat cells, indicating that downstream differentiation-dependent genes maintain responsiveness to regulators of adipogenesis. C/EBP alpha -expression also decreased with age in fat tissue from three different depots and in isolated fat cells. The overall level of C/EBP beta, which modulates C/EBP alpha -expression, did not change with age, but the truncated, dominant-negative C/EBP beta -liver inhibitory protein (LIP) isoform increased in cultured preadipocytes and isolated fat cells. Overexpression of C/EBP beta -LIP in preadipocytes from young rats impaired adipogenesis. C/EBP delta, which acts with full-length C/EBP beta to enhance adipogenesis, decreased with age. Thus processes intrinsic to adipose cells involving changes in C/EBP family members contribute to impaired adipogenesis and altered fat tissue function with aging. These effects are potentially reversible.