Mantha L, Russell J C, Brindley D N, Deshaies Y
Centre de recherche sur le métabolisme énergétique, Département d'anatomie et physiologie, Faculté de médecine, Université Laval, Québec, Canada.
Int J Obes Relat Metab Disord. 2002 Mar;26(3):308-17. doi: 10.1038/sj.ijo.0801882.
To characterize the developmental changes in adipose and muscle lipoprotein lipase (LPL) activity in the atherosclerosis-prone JCR:LA-corpulent rat, and to test the hypothesis that tissue-specific abnormalities in LPL activity precede the establishment of obesity.
Lean (+/?) and obese cp/cp male JCR:LA rats were studied at 4, 5 and 8 weeks of age, that is at the onset of obesity, and at a time when obesity is well established. Assessment was made of plasma variables related to glucose and lipid metabolism and of LPL activity in several adipose depots, skeletal muscles and the heart.
At week 4, body weights were identical in both genotypes and began to diverge at week 5. Eight-week-old cp/cp rats weighed 35% more than their lean counterparts. Perirenal and epididymal adipose depot weights were also identical in both genotypes at week 4 and began to increase in cp/cp rats at week 5, whereas the subcutaneous depot of 4-week-old cp/cp rats was slightly enlarged. At week 4, the cp/cp rats were hyperinsulinemic (5-fold), hyperleptinemic (30-fold) and hypertriglyceridemic (3-fold) compared to their lean counterparts, and their liver contained twice as much triglyceride. The 4-week-old cp/cp rats displayed 2-7-fold higher LPL specific activity in the various adipose depots compared to lean rats, and enzyme activity remained higher in obese than in lean rats at all subsequent ages. In contrast, LPL activity in the vastus lateralis, gastrocnemius and heart muscles of 4-week-old obese rats was approximately half that observed in lean animals.
Profound, persistent alterations in the tissue-specific modulation of LPL activity are established in the JCR:LA cp/cp rat prior to the development of frank obesity. The increase in adipose tissue LPL activity and its decrease in muscle tissues are likely to be related to the concomitant alterations in insulinemia and triglyceridemia, respectively. The pre-obesity, tissue-specific alterations in LPL activity may be considered as an integrated adaptation to increased lipid flux aimed at driving lipids toward storage sites and limiting their uptake by triglyceride-laden muscles.
描述易患动脉粥样硬化的JCR:LA肥胖大鼠脂肪和肌肉脂蛋白脂肪酶（LPL）活性的发育变化，并检验LPL活性的组织特异性异常先于肥胖发生这一假说。
对4周、5周和8周龄的瘦型（+/？）和肥胖型cp/cp雄性JCR:LA大鼠进行研究，即肥胖开始时以及肥胖确立时。评估与葡萄糖和脂质代谢相关的血浆变量以及几个脂肪库、骨骼肌和心脏中的LPL活性。
4周龄时，两种基因型的体重相同，5周龄时开始出现差异。8周龄的cp/cp大鼠比瘦型大鼠重35%。4周龄时，两种基因型的肾周和附睾脂肪库重量也相同，cp/cp大鼠在5周龄时开始增加，而4周龄cp/cp大鼠的皮下脂肪库略有增大。4周龄时，与瘦型大鼠相比，cp/cp大鼠出现高胰岛素血症（5倍）、高瘦素血症（30倍）和高甘油三酯血症（3倍），其肝脏中的甘油三酯含量是瘦型大鼠的两倍。与瘦型大鼠相比，4周龄cp/cp大鼠在各个脂肪库中的LPL比活性高2 - 7倍，在所有后续年龄段，肥胖大鼠的酶活性仍高于瘦型大鼠。相比之下，4周龄肥胖大鼠的股外侧肌、腓肠肌和心肌中的LPL活性约为瘦型动物的一半。
在JCR:LA cp/cp大鼠中，在明显肥胖发生之前，LPL活性的组织特异性调节就已出现深刻而持续的改变。脂肪组织中LPL活性的增加及其在肌肉组织中的降低可能分别与同时出现的胰岛素血症和甘油三酯血症改变有关。肥胖前LPL活性的组织特异性改变可被视为对脂质通量增加的一种综合适应，旨在将脂质导向储存部位并限制其被富含甘油三酯的肌肉摄取。
