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肥胖母亲在孕期和哺乳期补充褪黑素可改善雄性子代胰岛细胞组成和β细胞功能。

Obese mothers supplemented with melatonin during gestation and lactation ameliorate the male offspring's pancreatic islet cellular composition and beta-cell function.

机构信息

Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil.

Faculty of Nutrition, A Motta University, Rio de Janeiro, Brazil.

出版信息

J Dev Orig Health Dis. 2023 Aug;14(4):490-500. doi: 10.1017/S2040174423000168. Epub 2023 Jun 27.

DOI:10.1017/S2040174423000168
PMID:37366144
Abstract

Melatonin supplementation to obese mothers during gestation and lactation might benefit the pancreatic islet cellular composition and beta-cell function in male offspring adulthood. C57BL/6 females (mothers) were assigned to two groups ( = 20/each) based on their consumption in control (C 17% kJ as fat) or high-fat diet (HF 49% kJ as fat). Mothers were supplemented with melatonin (Mel) (10 mg/kg daily) during gestation and lactation, or vehicle, forming the groups ( = 10/each): C, CMel, HF, and HFMel. The male offspring were studied, considering they only received the C diet after weaning until three months old. The HF mothers and their offspring showed higher body weight, glucose intolerance, insulin resistance, and low insulin sensitivity than the C ones. However, HFMel mothers and their offspring showed improved glucose metabolism and weight loss than the HF ones. Also, the offspring's higher expressions of pro-inflammatory markers and endoplasmic reticulum (ER) stress were observed in HF but reduced in HFMel. Contrarily, antioxidant enzymes were less expressed in HF but improved in HFMel. In addition, HF showed increased beta-cell mass and hyperinsulinemia but diminished in HFMel. Besides, the beta-cell maturity and identity gene expressions diminished in HF but enhanced in HFMel. In conclusion, obese mothers supplemented with melatonin benefit their offspring's islet cell remodeling and function. In addition, improving pro-inflammatory markers, oxidative stress, and ER stress resulted in better glucose and insulin levels control. Consequently, pancreatic islets and functioning beta cells were preserved in the offspring of obese mothers supplemented with melatonin.

摘要

孕期和哺乳期肥胖母亲补充褪黑素可能有益于雄性后代成年时胰岛细胞组成和β细胞功能。将 C57BL/6 雌性(母亲)根据其在对照(C 17%热量来自脂肪)或高脂肪饮食(HF 49%热量来自脂肪)中的消耗分为两组(每组 20 只)。母亲在孕期和哺乳期补充褪黑素(Mel)(每天 10mg/kg)或载体,形成以下组(每组 10 只):C、CMel、HF 和 HFMel。雄性后代仅在断奶后接受 C 饮食直至三个月大,然后进行研究。与 C 组相比,HF 组的母亲和后代体重更高、葡萄糖耐量受损、胰岛素抵抗和胰岛素敏感性降低。然而,与 HF 组相比,HFMel 组的母亲和后代表现出改善的葡萄糖代谢和体重减轻。此外,在 HF 中观察到后代促炎标志物和内质网(ER)应激的表达增加,而在 HFMel 中则减少。相反,在 HF 中抗氧化酶表达减少,而在 HFMel 中则改善。此外,HF 显示β细胞质量增加和高胰岛素血症,但在 HFMel 中减少。此外,HF 中β细胞成熟和特征基因表达减少,而 HFMel 中增强。总之,肥胖母亲补充褪黑素有益于其后代胰岛细胞重塑和功能。此外,改善促炎标志物、氧化应激和 ER 应激可更好地控制血糖和胰岛素水平。因此,肥胖母亲补充褪黑素可保留其后代的胰岛和功能β细胞。

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