Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Sci Rep. 2018 Oct 3;8(1):14751. doi: 10.1038/s41598-018-32906-0.
Maternal diet plays a critical role in health development. Perinatal overnutrition induces metabolic dysfunctions and obesity in the offspring. Obesity is associated with endocannabinoid system (ECS) over activation and oxidative stress. Liver ECS activation induces hepatic steatosis, inflammation and fibrosis while the antagonism of cannabinoid receptors ameliorates these alterations. Here, we investigated the effect of perinatal maternal high-fat diet (HF, 29% of calories as fat) on the ECS and antioxidant system in liver of male and female adult rat offspring (180 days old). Maternal HF diet increased hepatic cannabinoid receptors, ECS metabolizing enzymes and triglyceride content, with male offspring more affected. ECS changes are likely independent of estradiol serum levels but associated with increased hepatic content of estrogen receptor, which can stimulate the expression of ECS components. Differently, maternal HF diet decreased the activity of the antioxidant enzymes glutathione peroxidase, superoxide dismutase and catalase, and increased oxidative stress markers in both sexes. Alterations in the redox homeostasis were associated with mitochondria damage but not with liver fibrosis. Our data suggest that maternal HF diet induces ECS over activation in adulthood, and that male offspring are at higher risk to develop liver disease compared with female rats.
母体饮食在健康发育中起着关键作用。围产期营养过剩会导致后代代谢功能紊乱和肥胖。肥胖与内源性大麻素系统（ECS）过度激活和氧化应激有关。肝脏 ECS 的激活会导致肝脂肪变性、炎症和纤维化，而大麻素受体的拮抗作用则可以改善这些改变。在这里，我们研究了围产期母体高脂肪饮食（HF，29%的热量来自脂肪）对雄性和雌性成年大鼠后代（180 天大）肝脏中 ECS 和抗氧化系统的影响。母体 HF 饮食增加了肝脏中的大麻素受体、ECS 代谢酶和甘油三酯含量，雄性后代受影响更大。ECS 的变化可能与雌二醇血清水平无关，但与肝内雌激素受体含量增加有关，后者可以刺激 ECS 成分的表达。相反，母体 HF 饮食降低了谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶等抗氧化酶的活性，并增加了两性的氧化应激标志物。氧化还原平衡的改变与线粒体损伤有关，但与肝纤维化无关。我们的数据表明，母体 HF 饮食会导致成年后 ECS 过度激活，而且雄性后代比雌性大鼠更容易患肝病。
