Novel progress has been made to understand the adverse pathophysiology in the pancreas of offspring exposed to overnutrition in utero. Our study is the first to evaluate whether the adverse effects of maternal overnutrition on offspring β-cell function are reversible or preventable through preconception maternal diet interventions. Herein, offspring mice were exposed in utero to one of the following: maternal normal-fat diet (NF group), maternal high-fat diet (HF group) or maternal diet transition from an HF to NF diet 9 weeks before pregnancy (H9N group). Offspring mice were subjected to postweaning HF diet for 12 weeks. HF offspring, but not H9N, displayed glucose intolerance and insulin resistance. HF male offspring had enlarged islet β-cells with reduced β-cell density, whereas, H9N male offspring did not show these changes. Co-immunofluorescent (Co-IF) staining of glucose transporter 2 (Glut2) and insulin (Ins) revealed significantly more Glut2⁺Ins⁻ cells, indicative of insulin degranulation, in HF male offspring but not H9N. In addition, Co-IF of insulin and p-H3S10 indicated that β cells of HF male offspring, but not H9N, had proliferation defects likely due to inhibited protein kinase B (AKT) phosphorylation. In summary, our study demonstrates that maternal H9N diet effectively prevents functional deterioration of β cells seen in HF male offspring by avoiding β-cell proliferation defects and degranulation.

在了解暴露于子宫内营养过剩的后代的胰腺的不良病理生理学方面取得了新进展。我们的研究是第一个评估母体营养过剩对后代 β 细胞功能的不利影响是否可以通过孕前母体饮食干预逆转或预防的研究。在这里，后代小鼠在子宫内暴露到以下之一：母亲正常脂肪饮食（NF 组）、母亲高脂肪饮食（HF 组）或孕前 9 周从 HF 饮食过渡到 NF 饮食的母亲饮食（H9N 组）。后代小鼠接受断奶后 HF 饮食 12 周。HF 后代，但不是 H9N，表现出葡萄糖耐受不良和胰岛素抵抗。HF 雄性后代的胰岛 β 细胞增大，β 细胞密度降低，而 H9N 雄性后代则没有这些变化。葡萄糖转运蛋白 2 (Glut2) 和胰岛素 (Ins) 的共免疫荧光 (Co-IF) 染色显示出明显更多的 Glut2 ⁺ Ins ^-HF 雄性后代而非 H9N 中的细胞，表明胰岛素脱颗粒。此外，胰岛素和 p-H3S10 的 Co-IF 表明 HF 雄性后代的 β 细胞（而非 H9N）具有增殖缺陷，这可能是由于蛋白激酶 B (AKT) 磷酸化受到抑制所致。总之，我们的研究表明，母体 H9N 饮食通过避免 β 细胞增殖缺陷和脱颗粒，有效地防止了 HF 雄性后代中 β 细胞的功能退化。