Barke R A, Brady P S, Brady L J
Department of Surgery, University of Minnesota, Minneapolis.
Surgery. 1991 Aug;110(2):285-94.
Cytokines have been implicated in the modulation of fat metabolism after sepsis. Carnitine palmitoyltransferase (CPT), the regulatory enzyme of hepatic mitochondrial long-chain fatty-acid oxidation, is involved in the control of hepatic fat oxidation in sepsis. Using either H4IIe rat hepatoma cells or rat hepatocytes in primary culture, we tested the hypothesis that interleukin-1-alpha (IL-1 alpha) would modulate CPT transcription (CPT mRNA), CPT translation (35S-methionine CPT protein incorporation), and hepatic mitochondrial oxidation of 1-Carbon 14-labeled (14C) palmitate to ketone bodies (acid soluble products). We showed that IL-1 alpha significantly increased CPT mRNA, 35S-methionine incorporation CPT protein, and hepatic mitochondrial oxidation of 1-14C-palmitate to acid soluble products. We further hypothesized that the Ca2+ second messenger system may play a role in the IL-1 alpha induction of hepatic CPT gene transcription. We showed that either calcium ionophore (A23187) or phorbol myristate acetate increased CPT gene transcription and that either calcium chelation, protein kinase C inhibition (acridine orange), or chronic exposure to phorbol myristate acetate significantly inhibited IL-1 alpha induction of CPT mRNA. We conclude that the IL-1 alpha increases in hepatic mitochondrial fatty-acid oxidation may be, in part, secondary to increased CPT gene transcription and translation and that the Ca2+ second messenger system may play an important role in IL-1 alpha induction of CPT gene transcription.
细胞因子已被证明参与脓毒症后脂肪代谢的调节。肉碱棕榈酰转移酶（CPT）是肝脏线粒体长链脂肪酸氧化的调节酶，参与脓毒症时肝脏脂肪氧化的控制。我们使用H4IIe大鼠肝癌细胞或原代培养的大鼠肝细胞，来验证白细胞介素-1α（IL-1α）是否会调节CPT转录（CPT mRNA）、CPT翻译（35S-甲硫氨酸CPT蛋白掺入）以及肝脏线粒体将1-碳-14标记（14C）的棕榈酸酯氧化为酮体（酸溶性产物）这一假说。我们发现IL-1α显著增加了CPT mRNA、35S-甲硫氨酸掺入CPT蛋白，以及肝脏线粒体将1-14C-棕榈酸酯氧化为酸溶性产物的能力。我们进一步推测Ca2+第二信使系统可能在IL-1α诱导肝脏CPT基因转录中发挥作用。我们发现钙离子载体（A23187）或佛波酯肉豆蔻酸酯均可增加CPT基因转录，而钙螯合、蛋白激酶C抑制（吖啶橙）或长期暴露于佛波酯肉豆蔻酸酯均显著抑制IL-1α诱导的CPT mRNA。我们得出结论，IL-1α导致肝脏线粒体脂肪酸氧化增加可能部分归因于CPT基因转录和翻译增加，并且Ca2+第二信使系统可能在IL-1α诱导CPT基因转录中起重要作用。
