Uptake of long chain free fatty acids is selectively up-regulated in adipocytes of Zucker rats with genetic obesity and non-insulin-dependent diabetes mellitus
Uptake of long chain free fatty acids is selectively up-regulated in adipocytes of Zucker rats with genetic obesity and non-insulin-dependent diabetes mellitus
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DOI：
10.1074/jbc.272.13.8830
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发表时间：
1997-03-28
影响因子：
4.8
通讯作者：
Isola, LM
中科院分区：
文献类型：
--
作者：
Berk, PD;Zhou, SL;Isola, LM
为了检查脂肪酸转运是否在肥胖症中异常，研究了成年雄性Wistar（+/+）、Zucker瘦（fa/+）和脂肪（fa/fa）以及Zucker糖尿病脂肪（ZDF）大鼠的肝细胞、心肌细胞和脂肪细胞摄取[H-3]油酸的动力学。在fa/fa和ZDF脂肪细胞中发现油酸摄取的组织特异性增加，其中V-max分别增加9倍（p < 0.005）和13倍（p < 0.001）。这一增加大大超过了肥胖动物脂肪细胞表面积的2倍增加，并且不是由继发于脂解增加的反式刺激引起的。通过北方杂交测定的脂肪细胞肿瘤坏死因子-α mRNA水平以+/+ < fa/fa < ZDF的顺序增加。还在20-24日龄雄性+/+、fa/+和fa/fa断奶仔猪的脂肪细胞中研究了油酸摄取。这些动物不肥胖，并且具有相等的血浆脂肪酸和葡萄糖水平。在+/+和fa/fa细胞中肿瘤坏死因子-cy mRNA水平也相似。然而，与+/+细胞相比，fa/fa中的V-max增加了2.9倍（p < 0.005）。这些研究表明：1）脂肪酸摄取的调节具有组织特异性; 2）脂肪细胞脂肪酸摄取的上调是Zucker fa/fa大鼠的早期事件。这些发现与任何特定脂肪酸转运蛋白的作用无关。脂肪细胞的三个假定的转运蛋白，线粒体天冬氨酸转氨酶，脂肪酸转位酶，脂肪酸转运蛋白（FATP）的mRNA水平也进行了测定;线粒体天冬氨酸转氨酶和FATP的mRNA与脂肪酸摄取强烈相关。
To examine whether fatty acid transport is abnormal in obesity, the kinetics of [H-3]oleate uptake by hepatocytes, cardiac myocytes, and adipocytes from adult male Wistar (+/+), Zucker lean (fa/+) and fatty (fa/fa), and Zucker diabetic fatty (ZDF) rats were studied. A tissue-specific increase in oleate uptake was found in fa/fa and ZDF adipocytes, in which the V-max was increased 9-fold (p < 0.005) and 13-fold (p < 0.001), respectively. This increase greatly exceeded the 2-fold increase in the surface area of adipocytes from obese animals, and did not result from trans-stimulation secondary to increased lipolysis. Adipocyte tumor necrosis factor-alpha mRNA levels, assayed by Northern hybridization, increased in the order +/+ < fa/fa < ZDF. Oleate uptake was also studied in adipocytes from 20-24-day-old male +/+, fa/+, and fa/fa weanlings. These animals were not obese, and had equivalent plasma fatty acid and glucose levels. Tumor necrosis factor-cy mRNA levels in +/+ and fa/fa cells also were similar. Nevertheless, V-max was increased 2.9-fold (p < 0.005) in fa/fa compared +/+ cells. These studies indicate 1) that regulation of fatty acid uptake is tissue-specific and 2) that up-regulation of adipocyte fatty acid uptake is an early event in Zucker fa/fa rats. These findings are independent of the role of any particular fatty acid transporter. Adipocyte mRNA levels of three putative transporters, mitochondrial aspartate aminotransferase, fatty acid translocase, and fatty acid transporting protein (FATP) were also determined; mitochondrial aspartate aminotransferase and FATP mRNAs correlated strongly with fatty acid uptake.