Picard Frédéric, Arsenijevic Denis, Richard Denis, Deshaies Yves
Centre de recherche de l'Hôpital Laval and Centre de recherche sur le métabolisme énergétique, Département d'anatomie et physiologie, Faculté de médecine, Université Laval, Québec, Québec, Canada G1K 7P4.
Clin Diagn Lab Immunol. 2002 Jul;9(4):771-6. doi: 10.1128/cdli.9.4.771-776.2002.
Infection of male Swiss Webster mice with Toxoplasma gondii or Neospora caninum leads to long-term alterations in energy balance. Following an initial 20 to 30% weight loss in all T. gondii-infected mice, half of the animals regain most of the lost weight (gainers), whereas the others maintain their low body weight (nongainers). Infection with N. caninum does not elicit weight loss. Lipoprotein lipase (LPL), the enzyme responsible for plasma triglyceride (TG) clearance and partitioning among tissues, is under tissue-specific modulation associated with energy balance. It is also a major determinant of infection-induced hypertriglyceridemia. This study aimed to assess the long-term modulation of adipose and muscle LPL activity in mice infected with T. gondii or N. caninum, to evaluate the effects of subsequent acute lipopolysaccharide (LPS) administration, and to relate LPL modulation in these conditions with infection-related changes in body weight gain. Twenty-eight days after infection, LPL activity in muscle of both gainer and nongainer T. gondii-infected mice was reduced by 40 to 50% compared with the levels in controls and N. caninum-infected mice, whereas LPL activity in adipose depots remained unchanged in all infected groups compared to the level in controls. LPS (from Escherichia coli, 100 ng/kg) injection induced a global reduction in adipose LPL in all groups, as assessed 90 min later. In both T. gondii-infected subgroups, muscle LPL was not further reduced by LPS treatment, whereas it was decreased by 40 to 50% in muscles of control and N. caninum-infected mice. Pre-LPS TG levels in plasma were similar in all groups. LPS greatly increased TG levels in plasma in both control and N. caninum-infected animals, whereas it did not alter those of T. gondii-infected gainer or nongainer animals. These results show that (i) independently of the extent of postinfection weight gain, long-term infection with T. gondii chronically reduces muscle LPL, which becomes unresponsive to acute endotoxemia; (ii) modulation of tissue LPL activity during chronic T. gondii infection favors TG partitioning towards adipose tissue; and (iii) skeletal muscle LPL is a key determinant of the acute response of triglyceridemia to LPS.
用刚地弓形虫或犬新孢子虫感染雄性瑞士韦伯斯特小鼠会导致能量平衡的长期改变。在所有感染刚地弓形虫的小鼠最初体重减轻20%至30%之后，一半的动物恢复了大部分减轻的体重（体重增加者），而其他动物则维持低体重（体重未增加者）。感染犬新孢子虫不会引起体重减轻。脂蛋白脂肪酶（LPL）是负责血浆甘油三酯（TG）清除及在各组织间分配的酶，其受到与能量平衡相关的组织特异性调节。它也是感染诱导的高甘油三酯血症的主要决定因素。本研究旨在评估感染刚地弓形虫或犬新孢子虫的小鼠脂肪和肌肉中LPL活性的长期调节情况，评估随后急性给予脂多糖（LPS）的影响，并将这些情况下的LPL调节与感染相关的体重增加变化联系起来。感染后28天，与对照组和感染犬新孢子虫的小鼠相比，感染刚地弓形虫的体重增加者和体重未增加者的肌肉中LPL活性降低了40%至50%，而与对照组相比，所有感染组脂肪库中的LPL活性保持不变。90分钟后评估发现，注射LPS（来自大肠杆菌，100 ng/kg）导致所有组的脂肪LPL整体降低。在两个感染刚地弓形虫的亚组中，LPS处理并未使肌肉LPL进一步降低，而在对照组和感染犬新孢子虫的小鼠肌肉中，LPL降低了40%至50%。所有组血浆中LPS处理前的TG水平相似。LPS使对照组和感染犬新孢子虫的动物血浆中的TG水平大幅升高，而对感染刚地弓形虫的体重增加者或体重未增加者的TG水平没有影响。这些结果表明：（i）无论感染后体重增加的程度如何，长期感染刚地弓形虫会慢性降低肌肉LPL，使其对急性内毒素血症无反应；（ii）慢性感染刚地弓形虫期间组织LPL活性的调节有利于TG向脂肪组织的分配；（iii）骨骼肌LPL是甘油三酯血症对LPS急性反应的关键决定因素。
