Department of Bioscience, Institute of Health and Society, Laboratory of Nutrition and Endocrine Physiology, Federal University of São Paulo, Santos, Brazil; Metabolic Research Laboratories and MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom.
Department of Bioscience, Institute of Health and Society, Laboratory of Nutrition and Endocrine Physiology, Federal University of São Paulo, Santos, Brazil.
J Nutr Biochem. 2024 Jul;129:109639. doi: 10.1016/j.jnutbio.2024.109639. Epub 2024 Apr 6.
This study aimed to investigate whether modifying the pre-gestational lipid content could mitigate metabolic damage in offspring from dams exposed to a high-fat (HF) diet before conception and during pregnancy and lactation, with a focus on sex-specific outcomes. Specific effects of maternal normolipidic diets on offspring were also assessed. Female Wistar rats received control (C) or HF diets before conception. During pregnancy and lactation, females were distributed in five groups: C-C, HF-HF, HF-C, HF-saturated (HF-S) or HF-polyunsaturated n-3 group (HF-P). Saturated and PUFA n-3 diets were normolipidic. In 21-day-old offspring, corporal parameters, adiposity, serum metabolites, OGTT, liver phenotype, and miR-34a-5p hepatic expression were determined. Pre-gestational HF diet impaired glycemic response in females, independent of any change in body weight. Female and male offspring from dams continuously exposed to HF diet exhibited hyperglycemia, increased adiposity, and disrupted serum lipid profiles. Male offspring showed increased hepatic fat accumulation and miR-34a-5p expression. Shifting maternal dietary lipid content to normolipidic diets restored offspring's phenotype; however, decreased SIRT1, IRβ and IRS1 expression in offspring from dams exposed to HF diet before conception suggested early indicators of glucose metabolism damage. Our findings indicated a pronounced metabolic impact on males. In conclusion, glucose tolerance impairment in females before conception disturbed intrauterine environment, influencing in offspring's phenotype. Modifying maternal dietary lipid content mitigated effects of pre-gestational HF diet exposure on young offspring. Nevertheless, decreased hepatic levels of critical insulin signaling proteins indicated that independently of the maternal diet, pre-existing HF diet-induced glucose intolerance before conception may adversely program the offspring's phenotype.
本研究旨在探讨在受孕前和妊娠及哺乳期暴露于高脂肪（HF）饮食的母鼠中，改变孕前的脂质含量是否可以减轻后代的代谢损伤，并特别关注性别特异性的结果。同时还评估了母体正常脂质饮食对后代的具体影响。雌性 Wistar 大鼠在受孕前接受对照（C）或 HF 饮食。在妊娠和哺乳期，雌性大鼠被分为五组：C-C、HF-HF、HF-C、HF-饱和（HF-S）或 HF-多不饱和 n-3 组（HF-P）。饱和和 PUFA n-3 饮食是正常脂质的。在 21 天大的后代中，测定了身体参数、肥胖程度、血清代谢物、OGTT、肝表型和 miR-34a-5p 肝表达。孕前 HF 饮食损害了雌性的血糖反应，而与体重变化无关。连续暴露于 HF 饮食的母鼠的雌性和雄性后代表现出高血糖、肥胖增加和血清脂质谱紊乱。雄性后代表现出肝脂肪堆积增加和 miR-34a-5p 表达增加。将母体饮食脂质含量转变为正常脂质饮食可恢复后代的表型；然而，在受孕前暴露于 HF 饮食的母鼠的后代中 SIRT1、IRβ 和 IRS1 表达降低，表明存在葡萄糖代谢损伤的早期指标。我们的研究结果表明，雄性的代谢影响更为显著。总之，受孕前雌性的葡萄糖耐量受损会扰乱宫内环境，影响后代的表型。改变母体饮食脂质含量可减轻受孕前 HF 饮食暴露对幼鼠的影响。然而，关键胰岛素信号蛋白在肝内水平降低表明，无论母体饮食如何，受孕前 HF 饮食诱导的葡萄糖耐量受损可能会对后代的表型产生不利影响。
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