Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Department of Pediatrics, Section of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Nutrients. 2020 Mar 14;12(3):767. doi: 10.3390/nu12030767.
Overweight and obesity accompanies up to 70% of pregnancies and is a strong risk factor for offspring metabolic disease. Maternal obesity-associated inflammation and lipid profile are hypothesized as important contributors to excess offspring liver and skeletal muscle lipid deposition and oxidative stress. Here, we tested whether dams expressing the fat-1 transgene, which endogenously converts omega-6 (n-6) to omega-3 (n-3) polyunsaturated fatty acid, could protect wild-type (WT) offspring against high-fat diet induced weight gain, oxidative stress, and disrupted mitochondrial fatty acid oxidation. Despite similar body mass at weaning, offspring from fat-1 high-fat-fed dams gained less weight compared with offspring from WT high-fat-fed dams. In particular, WT males from fat-1 high-fat-fed dams were protected from post-weaning high-fat diet induced weight gain, reduced fatty acid oxidation, or excess oxidative stress compared with offspring of WT high-fat-fed dams. Adult offspring of WT high-fat-fed dams exhibited greater skeletal muscle triglycerides and reduced skeletal muscle antioxidant defense and redox balance compared with offspring of WT dams on control diet. Fat-1 offspring were protected from the reduced fatty acid oxidation and excess oxidative stress observed in offspring of WT high-fat-fed dams. These results indicate that a maternal fat-1 transgene has protective effects against offspring liver and skeletal muscle lipotoxicity resulting from a maternal high-fat diet, particularly in males. Altering maternal fatty acid composition, without changing maternal dietary composition or weight gain with high-fat feeding, may highlight important strategies for n-3-based prevention of developmental programming of obesity and its complications.
超重和肥胖症伴随着高达 70%的妊娠，并成为后代代谢性疾病的强烈危险因素。母体肥胖相关的炎症和脂质谱被假设为导致后代肝脏和骨骼肌脂质沉积和氧化应激增加的重要因素。在这里，我们测试了表达 fat-1 转基因的母鼠是否可以保护野生型（WT）后代免受高脂肪饮食引起的体重增加、氧化应激和线粒体脂肪酸氧化受损的影响。尽管在断奶时体重相似，但高脂肪喂养的 fat-1 后代与高脂肪喂养的 WT 后代相比，体重增加较少。特别是，高脂肪喂养的 fat-1 雄性 WT 后代与高脂肪喂养的 WT 后代相比，免受断奶后高脂肪饮食引起的体重增加、脂肪酸氧化减少或过度氧化应激的影响。高脂肪喂养的 WT 后代的成年后代骨骼肌甘油三酯增加，骨骼肌抗氧化防御和氧化还原平衡减少，与控制饮食的 WT 后代的后代相比。fat-1 后代免受高脂肪喂养的 WT 后代观察到的脂肪酸氧化减少和过度氧化应激的影响。这些结果表明，母体 fat-1 转基因对母体高脂肪饮食引起的后代肝脏和骨骼肌脂肪毒性具有保护作用，特别是在雄性中。改变母体脂肪酸组成，而不改变母体饮食组成或高脂肪喂养时的体重增加，可能突出了基于 n-3 的肥胖及其并发症发育编程的重要预防策略。
