Programmed Upregulation of Adipogenic Transcription Factors in Intrauterine Growth-Restricted Offspring
Programmed Upregulation of Adipogenic Transcription Factors in Intrauterine Growth-Restricted Offspring
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DOI：
10.1177/1933719108318597
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发表时间：
2008-10-01
影响因子：
2.9
通讯作者：
Lane, Robert H.
中科院分区：
文献类型：
--
作者：
Desai, Mina;Han, Guang;Lane, Robert H.
由于脂肪生成增强导致程序性肥胖，因此对子宫内生长受限 (IUGR) 后代的脂肪生成和脂肪生成信号通路进行了检查。从妊娠 10 天到足月，有 50% 的小鼠随意进食（对照），或者 50% 的小鼠禁食 (IUGR)。幼崽被喂养并断奶，自由采食。测定 mRNA 和脂肪细胞大小（3 周和 9 个月）。一天大的 IUGR 雄性表现出过氧化物酶体增殖物激活受体 (PPAR gamma(2)) 的上调，包括调节 PPAR gamma 的上游因子和 RXR α（PPAR γ 与 RXR α 异二聚化）。细胞内脂肪分解酶（激素敏感性脂肪酶）下调。九个月大的 IUGR 雄性表现出脂肪生成和脂肪生成 (SREBP1c) 转录因子的上调，以及促进脂肪酸摄取（脂蛋白脂肪酶）和合成（脂肪酸合酶）的酶的上调，导致脂肪细胞肥大。 IUGR 男性肥胖发生之前脂肪生成信号级联的矛盾上调表明信号机制的早期变化。
As enhanced adipogenesis contributes to programmed obesity, adipogenic and lipogenic signaling pathways in intrauterine growth restricted (IUGR) offspring were examined. From 10 days to term gestation, rates received ad libitum food (control) or were 50% food-restricted (IUGR). Pups were nursed and weaned to ad libitum diet. mRNA and adipocyte cell size (3 weeks and 9 months) were determined. One-day-old IUGR males showed upregulation of peroxisome proliferator-activated receptor (PPAR gamma(2)), including upstream factors regulating PPAR gamma, and RXR alpha, with which PPAR gamma heterodimerizes. Intracellular lipolytic enzyme (hormone-sensitive lipase) was downregulated. Nine-month-old IUGR males showed upregulation of adipogenic and lipogenic (SREBP1c) transcription factors with upregulation of enzymes facilitating fatty acid uptake (lipoprotein lipase) and synthesis (fatty acid synthase), leading to hypertrophic adipoctyes. Paradoxical upregulation of adipogensis signaling cascade prior to the development of obesity in IUGR males suggests early changes in signaling mechanisms.