Arsenijevic D, Bilbao F D, Giannakopoulos P, Girardier L, Samec S, Richard D
Physiology and Animal Husbandary, Institute of Physiology and Animal Science, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, Schwerzenbach 8603, Switzerland.
Eur Cytokine Netw. 2001 Jul-Sep;12(3):518-27.
Toxoplasma gondii (Me49 strain) infection into Swiss Webster mice is followed by hypermetabolism and weight loss in the acute phase lasting 14 days. In the subsequent chronic phase of infection, mice showed either a resolution of hypermetabolism and partial weight recovery (Gainers) or persistent hypermetabolism, with stable weight loss (Non-Gainers). The hypermetabolic response was not associated with an augmentation in the thermogenic uncoupling protein 1 (UCP1) mRNA expression in interscapular brown adipose tissue (BAT), but rather UCP1 expression was reduced. Hypermetabolism is associated with high lipid oxidation as attested by a low respiratory quotient (RQ). Neither BAT nor sympathetic nervous system appear to be involved in the increased lipid utilization, since propranolol did not increase the lower RQ in infected mice. The mitochondrial lipid oxidation blocker mercaptoacetate did not reestablish the respiratory quotient RQ in acute infection (on day 4) and in chronically infected Non-Gainer mice. This suggests an important extra-mitochondrial mechanism of lipid oxidation. Increased lipid peroxidation was detected especially in serum, lung, spleen and liver, which are rich in macrophage-type cells. Following infection peritoneal macrophages exhibited an enhanced capacity to produce reactive oxygen species (ROS). Using IFN-gamma knockout mice we observed that not only the hypermetabolic response was ablated in these mice but there was not a marked increase in ROS production or preferential oxidation/peroxidation of lipids in the acute phase of infection prior to the cachectic phase. The present study described a novel hypermetabolic mechanism involving enhanced lipid peroxidation dependent on IFN-gamma, especially associated with tissues rich in macrophages.
将刚地弓形虫（Me49株）感染瑞士韦伯斯特小鼠后，在持续14天的急性期会出现代谢亢进和体重减轻。在随后的慢性感染阶段，小鼠要么代谢亢进消退且体重部分恢复（体重增加组），要么持续代谢亢进并伴有体重稳定减轻（体重未增加组）。代谢亢进反应与肩胛间棕色脂肪组织（BAT）中产热解偶联蛋白1（UCP1）mRNA表达的增加无关，相反，UCP1表达降低。代谢亢进与低呼吸商（RQ）所证明的高脂质氧化有关。BAT和交感神经系统似乎均未参与脂质利用的增加，因为普萘洛尔并未提高感染小鼠较低的RQ。线粒体脂质氧化阻断剂巯基乙酸在急性感染（第4天）和慢性感染的体重未增加组小鼠中并未恢复呼吸商RQ。这表明脂质氧化存在重要的线粒体外机制。尤其在富含巨噬细胞类型细胞的血清、肺、脾和肝脏中检测到脂质过氧化增加。感染后，腹腔巨噬细胞产生活性氧（ROS）的能力增强。使用干扰素-γ基因敲除小鼠，我们观察到不仅这些小鼠的代谢亢进反应消失，而且在恶病质阶段之前的急性感染期，ROS产生没有明显增加，脂质也没有优先氧化/过氧化。本研究描述了一种新的代谢亢进机制，该机制涉及依赖干扰素-γ的脂质过氧化增强，尤其与富含巨噬细胞的组织有关。
