Ghosh S, O'Connell J F, Carlson O D, González-Mariscal I, Kim Y, Moaddel R, Ghosh P, Egan J M
National Institute on Aging, Laboratory of Clinical Investigation National Institutes of Health Baltimore Maryland USA.
Pharmacology University of Pennsylvania Philadelphia Pennsylvania USA.
Obes Sci Pract. 2019 Jul 16;5(4):383-394. doi: 10.1002/osp4.344. eCollection 2019 Aug.
Linoleic acid (LA) is an essential fatty acid involved in the biosynthesis of arachidonic acid and prostaglandins. LA is known to induce obesity and insulin resistance. In this study, two concentrations of LA with or without added glucose (G) were fed to mice to investigate their effects on endocannabinoid (EC) biology.
Four groups of C57BL/6 mice were provided with diets containing 1% or 8% LA with or without added G (LAG) for 8 weeks. Body weights, food intake, circulating glucose and insulin levels were measured throughout the study. Following euthanasia, plasma, bowel and hepatic ECs, monoacylglycerol lipase and fatty acid amide hydroxylase protein levels (enzymes responsible for EC degradation) and transcriptional activity of PPARα in liver were quantified. Liver was probed for evidence of insulin receptor activity perturbation.
Increasing dietary LA from 1% to 8% significantly increased circulating, small bowel and hepatic ECs. 1%LAG fed mice had lowest feed efficiency, and only liver levels of both ECs were reduced by addition of G. Addition of G to 1% LA diets resulted in elevated monoacylglycerol lipase and fatty acid amide hydroxylase protein levels ( < 0.001 and < 0.001, respectively) in liver due to increased transcriptional activity of PPARα ( < 0.05). The reduced EC levels with addition of G also correlated with a measure of enhanced insulin action.
In conclusion, body weight of mice is influenced by the source of calorie intake. Furthermore, tissue EC/g are dependent on tissue-specific synthesis and degradation that are modulated by dietary LA and G which also influence food efficiency, and down-stream insulin signalling pathways. The findings could potentially be useful information for weight management efforts in humans.
亚油酸（LA）是一种必需脂肪酸，参与花生四烯酸和前列腺素的生物合成。已知LA会诱发肥胖和胰岛素抵抗。在本研究中，给小鼠喂食两种浓度的LA，添加或不添加葡萄糖（G），以研究其对内源性大麻素（EC）生物学的影响。
四组C57BL/6小鼠被给予含有1%或8%LA、添加或不添加G（LAG）的饮食，持续8周。在整个研究过程中测量体重、食物摄入量、循环葡萄糖和胰岛素水平。安乐死后，对血浆、肠道和肝脏中的EC、单酰甘油脂肪酶和脂肪酸酰胺水解酶蛋白水平（负责EC降解的酶）以及肝脏中PPARα的转录活性进行定量。检测肝脏中胰岛素受体活性扰动的证据。
将饮食中的LA从1%增加到8%显著增加了循环、小肠和肝脏中的EC。喂食1%LAG的小鼠饲料效率最低，仅添加G可降低肝脏中两种EC的水平。在1%LA饮食中添加G会导致肝脏中单酰甘油脂肪酶和脂肪酸酰胺水解酶蛋白水平升高（分别为<0.001和<0.001），这是由于PPARα转录活性增加（<0.05）。添加G后EC水平降低也与胰岛素作用增强的指标相关。
总之，小鼠的体重受卡路里摄入来源的影响。此外，组织中的EC/g取决于组织特异性合成和降解，其受饮食中的LA和G调节，这也会影响食物效率和下游胰岛素信号通路。这些发现可能对人类体重管理工作有潜在的有用信息。
