Nonogaki K, Moser A H, Pan X M, Staprans I, Grunfeld C, Feingold K R
Department of Medicine, University of California, San Francisco, 94143, USA.
J Lipid Res. 1995 Sep;36(9):1987-95.
The host response to infection is frequently accompanied by changes in lipid metabolism. Previous studies have shown that endotoxin (LPS), a component of the cell wall of gram-negative bacteria, increases serum lipid levels. In this study, we demonstrate that lipoteichoic acid (LTA), a component of the cell membrane of gram-positive bacteria, also increases serum lipid levels in rats in a dose-dependent manner (0.1-300 micrograms/200 g body weight). Serum triglyceride levels increased within 2 h after LTA administration with peak values at 4 h (2-fold increase). Serum cholesterol levels also increased but the effect was delayed occurring at 16 h and was relatively small (1.2-fold increase). LTA (10 micrograms/200 g BW) did not decrease adipose tissue lipoprotein lipase activity or the clearance of triglyceride-rich lipoproteins. Rather, the LTA-induced hypertriglyceridemia is due to an increase in hepatic triglyceride secretion. LTA stimulates both hepatic de novo fatty acid synthesis and lipolysis. The increased delivery of free fatty acids to the liver plays a major role in the LTA-induced hypertriglyceridemia. Pretreatment with phentolamine, an alpha-adrenergic receptor antagonist, and alprenolol, a beta-adrenergic receptor antagonist, or phentolamine alone significantly suppressed the hypertriglyceridemia induced by LTA. These adrenergic inhibitors had no significant effect on the increase in lipolysis. These results indicate that catecholamines are involved in mediating the LTA-induced increase in hepatic triglyceride secretion via alpha-adrenergic receptors. These changes in lipid metabolism may play an important role in the organism's response to gram-positive infection.
机体对感染的反应常常伴随着脂质代谢的变化。先前的研究表明，内毒素（LPS）作为革兰氏阴性菌细胞壁的一种成分，会使血清脂质水平升高。在本研究中，我们证明了脂磷壁酸（LTA）作为革兰氏阳性菌细胞膜的一种成分，也能以剂量依赖的方式（0.1 - 300微克/200克体重）使大鼠血清脂质水平升高。给予LTA后2小时内血清甘油三酯水平升高，4小时达到峰值（升高2倍）。血清胆固醇水平也升高，但作用出现延迟，在16小时时升高，且升高幅度相对较小（升高1.2倍）。LTA（10微克/200克体重）并未降低脂肪组织脂蛋白脂肪酶活性或富含甘油三酯脂蛋白的清除率。相反，LTA诱导的高甘油三酯血症是由于肝脏甘油三酯分泌增加所致。LTA刺激肝脏从头合成脂肪酸和脂肪分解。游离脂肪酸向肝脏的输送增加在LTA诱导的高甘油三酯血症中起主要作用。用α - 肾上腺素能受体拮抗剂酚妥拉明和β - 肾上腺素能受体拮抗剂阿普洛尔预处理，或单独用酚妥拉明预处理，均能显著抑制LTA诱导的高甘油三酯血症。这些肾上腺素能抑制剂对脂肪分解的增加无显著影响。这些结果表明，儿茶酚胺通过α - 肾上腺素能受体参与介导LTA诱导的肝脏甘油三酯分泌增加。脂质代谢的这些变化可能在机体对革兰氏阳性菌感染的反应中起重要作用。
