Simino Laís Angélica de Paula, Panzarin Carolina, Torsoni Marcio Alberto, Ignácio-Souza Letícia Martins, Milanski Marciane, Torsoni Adriana Souza
Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas - UNICAMP, Limeira, São Paulo, Brazil.
J Dev Orig Health Dis. 2021 Aug;12(4):660-670. doi: 10.1017/S204017442000094X. Epub 2020 Oct 7.
The rising rate of childhood overweight follows the increase in maternal obesity, since perinatal events impact offspring in a diversity of metabolic disorders. Despite many studies that have linked dietary consumption, overnutrition, or maternal obesity as the mediators of fetal metabolic programming, there are gaps regarding the knowledge about the contribution of different maternal phenotypes to the development of metabolic disturbances in offspring. This study aimed to investigate whether maternal high-fat diet (HFD) consumption without the development of the obese phenotype would protect offspring from metabolic disturbances. Female mice were fed standard chow diet or a HFD for 4 weeks before mating. HFD females were classified into obesity-resistant (OR) or obesity-prone (OP), according to weight gain. OP females presented with higher adiposity, fasting serum glucose and insulin, cholesterol and non-esterified fatty acid (NEFA). Newborn offspring from OP dams showed higher serum glucose and insulin and alteration in hepatic gene expression that may have contributed to the rise in hepatic fat content and decline of glycogen levels in the liver. Despite offspring from OR and OP females having showed similar growth after the day of delivery, offspring from OP females had higher caloric intake, fasting glucose, serum triglycerides and altered hepatic gene expression, as well as glucose and pyruvate intolerance and lower insulin sensitivity at d28 compared with offspring from OR females. Maternal pre-pregnancy serum glucose, insulin, and NEFA positively correlated with serum glucose and fat liver content and negatively correlated with hepatic glycogen in offspring. In conclusion, our results show that maternal resistance to diet-induced obesity partially protects offspring from early metabolic disturbances.
儿童超重率的上升与母亲肥胖率的增加同步，因为围产期事件会影响后代出现多种代谢紊乱。尽管许多研究将饮食摄入、营养过剩或母亲肥胖视为胎儿代谢编程的介导因素，但关于不同母亲表型对后代代谢紊乱发展的贡献，仍存在知识空白。本研究旨在调查母亲食用高脂肪饮食（HFD）但未出现肥胖表型是否能保护后代免受代谢紊乱影响。雌性小鼠在交配前4周喂食标准饲料或HFD。根据体重增加情况，将食用HFD的雌性小鼠分为抗肥胖（OR）或易肥胖（OP）两类。OP雌性小鼠表现出更高的肥胖程度、空腹血清葡萄糖和胰岛素水平、胆固醇和非酯化脂肪酸（NEFA）水平。来自OP母鼠的新生后代血清葡萄糖和胰岛素水平更高，肝脏基因表达发生改变，这可能导致肝脏脂肪含量增加和肝脏糖原水平下降。尽管OR和OP雌性小鼠的后代在出生后生长情况相似，但与OR雌性小鼠的后代相比，OP雌性小鼠的后代在第28天热量摄入更高、空腹血糖和血清甘油三酯水平更高、肝脏基因表达改变，以及葡萄糖和丙酮酸不耐受且胰岛素敏感性更低。母亲孕前血清葡萄糖、胰岛素和NEFA水平与后代血清葡萄糖和脂肪肝含量呈正相关，与后代肝脏糖原呈负相关。总之，我们的结果表明，母亲对饮食诱导肥胖的抵抗力可部分保护后代免受早期代谢紊乱影响。
