Picard F, Richard D, Huang Q, Deshaies Y
Center for Research on Energy Metabolism, School of Medicine, Laval University, Québec, Canada.
Int J Obes Relat Metab Disord. 1998 Nov;22(11):1088-95. doi: 10.1038/sj.ijo.0800732.
To characterize the adaptations of lipid metabolism, with special emphasis on tissue lipoprotein lipase, to negative energy balance brought by chronic treatment of obese ob/ob mice with leptin.
According to a 2 x 2 factorial analysis, lean and obese C57BL/6J mice were subcutaneously infused with leptin (100 micrograms.kg-1.day-1) or vehicle (phosphate-buffered saline) during seven days.
Cumulative food intake and final body weight of vehicle-infused obese mice were twofold higher than in lean controls. Leptin decreased cumulative food intake and body weight of obese, but not lean mice. Lipoprotein lipase (LPL) activity in white inguinal and epididymal and brown interscapular adipose tissues of control obese mice was at least twofold higher than in lean mice, but comparable in the vastus lateralis muscle. Leptin treatment of obese mice significantly lowered LPL activity to that of lean mice in all tissues examined. Vehicle-infused obese mice had higher liver triglyceride content and were hypertriglyceridemic compared to lean mice, and triglyceride concentrations in plasma and liver were decreased proportionally after leptin treatment. Leptin lowered glycemia and insulinemia of obese mice to lean levels and decreased plasma corticosterone. Leptin infusion had no notable effect on tissue lipoprotein lipase nor plasma variables of lean mice.
Leptin infusion abolished hyperinsulinemia in the ob/ob mouse, an effect that was probably responsible for the concomitant normalization of adipose LPL activity. This study shows that decreased LPL activity, plasma triglyceride concentrations and hepatic triglyceride production constitute some of the adaptive peripheral adaptations of lipid metabolism, which accompany the reduction in fat mass accretion brought by leptin treatment of the obese ob/ob mouse.
研究脂质代谢的适应性变化，特别关注组织脂蛋白脂肪酶，以探讨瘦素长期治疗肥胖ob/ob小鼠所导致的负能量平衡。
根据2×2析因分析，将瘦和肥胖的C57BL/6J小鼠在7天内皮下注射瘦素（100微克·千克⁻¹·天⁻¹）或赋形剂（磷酸盐缓冲盐水）。
注射赋形剂的肥胖小鼠的累积食物摄入量和最终体重比瘦素对照组高两倍。瘦素降低了肥胖小鼠而非瘦素小鼠的累积食物摄入量和体重。对照肥胖小鼠的腹股沟白色、附睾白色和肩胛间棕色脂肪组织中的脂蛋白脂肪酶（LPL）活性至少比瘦素小鼠高两倍，但在股外侧肌中相当。瘦素治疗肥胖小鼠后，所有检测组织中的LPL活性均显著降低至瘦素小鼠水平。与瘦素小鼠相比，注射赋形剂的肥胖小鼠肝脏甘油三酯含量更高且具有高甘油三酯血症，瘦素治疗后血浆和肝脏中的甘油三酯浓度成比例降低。瘦素将肥胖小鼠的血糖和胰岛素血症降低至瘦素小鼠水平，并降低了血浆皮质酮。瘦素注射对瘦素小鼠的组织脂蛋白脂肪酶和血浆变量无显著影响。
瘦素注射消除了ob/ob小鼠的高胰岛素血症，这一效应可能是脂肪组织LPL活性同时恢复正常的原因。本研究表明，LPL活性降低、血浆甘油三酯浓度和肝脏甘油三酯生成减少是脂质代谢的一些适应性外周变化，这些变化伴随着瘦素治疗肥胖ob/ob小鼠所带来的脂肪量增加减少。
