Huggins Kevin W, Boileau Amy C, Hui David Y
Center for Lipid and Arteriosclerosis Studies, Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Am J Physiol Endocrinol Metab. 2002 Nov;283(5):E994-E1001. doi: 10.1152/ajpendo.00110.2002.
Group 1B phospholipase A2 (PLA2) is an abundant lipolytic enzyme that is well characterized biochemically and structurally. Because of its high level of expression in the pancreas, it has been presumed that PLA2 plays a role in the digestion of dietary lipids, but in vivo data have been lacking to support this theory. Our initial study on mice lacking PLA2 demonstrated no abnormalities in dietary lipid absorption in mice consuming a chow diet. However, the effects of PLA2 deficiency on animals consuming a high-fat diet have not been studied. To investigate this, PLA2(+/+) and PLA2(-/-) mice were fed a western diet for 16 wk. The results showed that PLA2(-/-) mice were resistant to high-fat diet-induced obesity. This observed weight difference was due to decreased adiposity present in the PLA2(-/-) mice. Compared with PLA2(+/+) mice, the PLA2(-/-) mice had 60% lower plasma insulin and 72% lower plasma leptin levels after high-fat diet feeding. The PLA2(-/-) mice also did not exhibit impaired glucose tolerance associated with the development of obesity-related insulin resistance as observed in the PLA2(+/+) mice. To investigate the mechanism by which PLA(2)(-/-) mice exhibit decreased weight gain while on a high-fat diet, fat absorption studies were performed. The PLA(2)(-/-) mice displayed 50 and 35% decreased plasma [(3)H]triglyceride concentrations 4 and 6 h, respectively, after feeding on a lipid-rich meal containing [(3)H]triolein. The PLA(2)(-/-) mice also displayed increased lipid content in the stool, thus indicating decreased fat absorption in these animals. These results suggest a novel role for PLA(2) in the protection against diet-induced obesity and obesity-related insulin resistance, thereby offering a new target for treatment of obesity and diabetes.
1B组磷脂酶A2（PLA2）是一种丰富的脂解酶，在生化和结构方面都有充分的表征。由于其在胰腺中的高表达水平，人们推测PLA2在膳食脂质的消化中起作用，但一直缺乏体内数据来支持这一理论。我们最初对缺乏PLA2的小鼠的研究表明，食用普通饮食的小鼠在膳食脂质吸收方面没有异常。然而，尚未研究PLA2缺乏对食用高脂饮食动物的影响。为了对此进行研究，给PLA2(+/+)和PLA2(-/-)小鼠喂食西式饮食16周。结果显示，PLA2(-/-)小鼠对高脂饮食诱导的肥胖具有抗性。观察到的体重差异是由于PLA2(-/-)小鼠体内脂肪减少所致。与PLA2(+/+)小鼠相比，高脂饮食喂养后，PLA2(-/-)小鼠的血浆胰岛素水平低60%，血浆瘦素水平低72%。PLA2(-/-)小鼠也没有表现出如PLA2(+/+)小鼠中观察到的与肥胖相关的胰岛素抵抗发展相关的葡萄糖耐量受损。为了研究PLA2(-/-)小鼠在高脂饮食时体重增加减少的机制，进行了脂肪吸收研究。在喂食含有[3H]三油酸甘油酯的富含脂质的餐后4小时和6小时，PLA2(-/-)小鼠的血浆[3H]甘油三酯浓度分别降低了50%和35%。PLA2(-/-)小鼠的粪便中脂质含量也增加，从而表明这些动物的脂肪吸收减少。这些结果表明PLA2在预防饮食诱导的肥胖和肥胖相关的胰岛素抵抗中具有新的作用，从而为肥胖和糖尿病的治疗提供了一个新的靶点。
