de Paula Simino Laís Angélica, de Fante Thaís, Figueiredo Fontana Marina, Oliveira Borges Fernanda, Torsoni Márcio Alberto, Milanski Marciane, Velloso Lício Augusto, Souza Torsoni Adriana
Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas -UNICAMP, Limeira, São Paulo Brazil.
Laboratory of Cell Signaling, Faculty of Medical Sciences, University Of Campinas - UNICAMP, Campinas, São Paulo Brazil.
Nutr Metab (Lond). 2017 Feb 20;14:16. doi: 10.1186/s12986-017-0168-4. eCollection 2017.
Nutritional status in early life is critically involved in the metabolic phenotype of offspring. However the changes triggered by maternal consumption of high-fat diet (HFD) in pre- or postnatal period should be better understood. Here we evaluated whether maternal HFD consumption during gestation and lactation could differently affect liver miR-122 and miR-370 expression leading to metabolic damages observed in offspring. Moreover, we investigate whether early overnutrition program offspring to more harmful response to HFD in later life.
Female mice were fed either a standard chow (SC) diet or a HFD three weeks before and during mating, gestation and/or lactation. Offspring were evaluated on the delivery day (d0), in a cross-fostering model at day 28 (d28) and in adult life, after a re-challenge with a HFD (d82).
In vitro analysis using liver cell line showed that palmitate could induced decrease in miR-122 and increase in miR-370 expression. Newborn pups (d0) from obese dams showed a decrease in lipid oxidation markers ( and ), an increase in triacylglycerol synthesis markers ( and ), as well as lower miR-122 and higher miR-370 hepatic content that was inversely correlated to maternal serum NEFA and TAG. Pups fostered to SC dams presented an increase in body weight and / expression at d28 compared to pups fostered to HFD dams and an inverse correlation was observed between miR-122 hepatic expression and offspring serum TAG. In adult life (d82), the reintroduction of HFD resulted in higher body weight gain and hepatic lipid content. These effects were accompanied by impairment in lipid and glucose metabolism, demonstrated by reduced / and increased / expression, lower glucose tolerance and insulin sensitivity.
Our data suggest that both gestational and lactation overnutrition results in metabolic changes that can permanently alter lipid homeostasis in offspring. The presence of fatty acids in maternal blood and milk seem to be responsible for modulating the expression of and , which are involved in liver metabolism. These alterations significantly increase susceptibility to obesity and ectopic lipid accumulation and lead to a more harmful response to HFD in offspring.
生命早期的营养状况与后代的代谢表型密切相关。然而，对于孕期或产后母体高脂饮食（HFD）引发的变化，仍需深入了解。在此，我们评估了孕期和哺乳期母体摄入HFD是否会对肝脏miR-122和miR-370表达产生不同影响，进而导致后代出现代谢损伤。此外，我们还研究了早期营养过剩是否会使后代在成年后对HFD产生更有害的反应。
雌性小鼠在交配前、交配期间、孕期和/或哺乳期的前三周分别喂食标准饲料（SC）或HFD。在分娩日（d0）、28日（d28）的交叉寄养模型以及成年后再次给予HFD刺激（d82）时对后代进行评估。
使用肝细胞系进行的体外分析表明，棕榈酸可诱导miR-122表达降低，miR-370表达升高。肥胖母鼠的新生幼崽（d0）脂质氧化标志物（和）减少，三酰甘油合成标志物（和）增加，肝脏中miR-122含量降低，miR-370含量升高，且与母体血清非酯化脂肪酸（NEFA）和甘油三酯（TAG）呈负相关。与寄养于HFD母鼠的幼崽相比，寄养于SC母鼠的幼崽在d28时体重增加，/表达升高，且肝脏miR-122表达与后代血清TAG呈负相关。在成年期（d82），重新给予HFD会导致体重增加和肝脏脂质含量升高。这些影响伴随着脂质和葡萄糖代谢受损，表现为/降低、/表达升高、葡萄糖耐量降低和胰岛素敏感性降低。
我们的数据表明，孕期和哺乳期营养过剩均会导致代谢变化，从而永久性改变后代的脂质稳态。母体血液和乳汁中的脂肪酸似乎负责调节参与肝脏代谢的和的表达。这些改变显著增加了后代对肥胖和异位脂质积累的易感性，并导致其对HFD产生更有害的反应。
