Brass E P, Vetter W H
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106-4981.
Biochem J. 1994 Jul 1;301 ( Pt 1)(Pt 1):193-7. doi: 10.1042/bj3010193.
The Kupffer-cell products interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) have been shown to stimulate hepatic lipogenesis in vivo. Studies were performed to define the direct effects of these cytokines on lipogenesis in primary-culture rat hepatocytes. Hepatocytes were cultured in the presence of IL-6 or TNF-alpha for periods of 24-72 h. IL-6 increased hepatocyte protein content per microgram of DNA. IL-6 also caused a dose- and time-dependent induction of hepatocyte capacity for incorporation of [2-14C]pyruvate into fatty acids (56% increase by 12.5 ng/ml IL-6 after 72 h of cytokine exposure). This increase in cellular lipogenic capacity was confirmed by using 3H2O incorporation into fatty acids as tracer. TNF-alpha did not increase hepatocyte lipogenesis. In contrast with studies in vivo, neither IL-6 nor TNF-alpha had any acute (2 h of exposure) effects on rates of lipogenesis. Both IL-6 and TNF-alpha are known to increase macrophage prostaglandin synthesis acutely. The prostaglandin E agonist misoprostol free acid (0.1 microM) acutely increased hepatocyte lipogenic rates by 14%. Thus, IL-6 can directly induce hepatocyte lipogenic capacity, and E-series prostaglandins can antagonize the acute inhibition of lipogenesis by glucagon. The observations provide further evidence for the role of Kupffer-cell products in the regulation of hepatocyte metabolism.
库普弗细胞产生的白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）已被证明在体内可刺激肝脏脂肪生成。本研究旨在确定这些细胞因子对原代培养大鼠肝细胞脂肪生成的直接影响。将肝细胞在IL-6或TNF-α存在的情况下培养24 - 72小时。IL-6增加了每微克DNA的肝细胞蛋白质含量。IL-6还引起肝细胞将[2-¹⁴C]丙酮酸掺入脂肪酸的能力呈剂量和时间依赖性诱导（细胞因子暴露72小时后，12.5 ng/ml IL-6使掺入量增加56%）。通过使用³H₂O掺入脂肪酸作为示踪剂，证实了细胞脂肪生成能力的增加。TNF-α未增加肝细胞脂肪生成。与体内研究相反，IL-6和TNF-α对脂肪生成速率均无任何急性（暴露2小时）影响。已知IL-6和TNF-α均可急性增加巨噬细胞前列腺素合成。前列腺素E激动剂米索前列醇游离酸（0.1 μM）可使肝细胞脂肪生成速率急性增加14%。因此，IL-6可直接诱导肝细胞脂肪生成能力，而E系列前列腺素可拮抗胰高血糖素对脂肪生成的急性抑制作用。这些观察结果为库普弗细胞产物在肝细胞代谢调节中的作用提供了进一步证据。
