Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain.
Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain.
Front Endocrinol (Lausanne). 2021 Dec 16;12:796661. doi: 10.3389/fendo.2021.796661. eCollection 2021.
Dietary intervention is a common tactic employed to curtail the current obesity epidemic. Changes in nutritional status alter metabolic hormones such as insulin or leptin, as well as the insulin-like growth factor (IGF) system, but little is known about restoration of these parameters after weight loss in obese subjects and if this differs between the sexes, especially regarding the IGF system. Here male and female mice received a high fat diet (HFD) or chow for 8 weeks, then half of the HFD mice were changed to chow (HFDCH) for 4 weeks. Both sexes gained weight (p < 0.001) and increased their energy intake (p < 0.001) and basal glycemia (p < 0.5) on the HFD, with these parameters normalizing after switching to chow but at different rates in males and females. In both sexes HFD decreased hypothalamic NPY and AgRP (p < 0.001) and increased POMC (p < 0.001) mRNA levels, with all normalizing in HFDCH mice, whereas the HFD-induced decrease in ObR did not normalize (p < 0.05). All HFD mice had abnormal glucose tolerance tests (p < 0.001), with males clearly more affected, that normalized when returned to chow. HFD increased insulin levels and HOMA index (p < 0.01) in both sexes, but only HFDCH males normalized this parameter. Returning to chow normalized the HFD-induced increase in circulating leptin (p < 0.001), total IGF1 (p < 0.001), IGF2 (p < 0.001, only in females) and IGFBP3 (p < 0.001), whereas free IGF1 levels remained elevated (p < 0.01). In males IGFBP2 decreased with HFD and normalized with chow (p < 0.001), with no changes in females. Although returning to a healthy diet improved of most metabolic parameters analyzed, fIGF1 levels remained elevated and hypothalamic ObR decreased in both sexes. Moreover, there was sex differences in both the response to HFD and the switch to chow including circulating levels of IGF2 and IGFBP2, factors previously reported to be involved in glucose metabolism. Indeed, glucose metabolism was also differentially modified in males and females, suggesting that these observations could be related.
饮食干预是一种常见的策略，用于遏制当前的肥胖流行。营养状况的改变会改变代谢激素，如胰岛素或瘦素，以及胰岛素样生长因子（IGF）系统，但对于肥胖患者减肥后这些参数的恢复情况以及这种恢复是否存在性别差异，知之甚少，特别是关于 IGF 系统。在这里，雄性和雌性小鼠接受高脂肪饮食（HFD）或标准饮食 8 周，然后一半的 HFD 小鼠改为标准饮食 4 周。两种性别的小鼠体重均增加（p<0.001），能量摄入（p<0.001）和基础血糖（p<0.5）均增加，而切换到标准饮食后这些参数恢复正常，但在雄性和雌性中的恢复速度不同。在两种性别中，HFD 降低了下丘脑 NPY 和 AgRP（p<0.001）并增加了 POMC（p<0.001）mRNA 水平，在 HFDCH 小鼠中所有这些水平均恢复正常，而 HFD 诱导的 ObR 减少并未恢复正常（p<0.05）。所有 HFD 小鼠的葡萄糖耐量试验均异常（p<0.001），雄性小鼠受影响更为明显，而当它们回到标准饮食时，这种情况恢复正常。HFD 增加了两种性别的胰岛素水平和 HOMA 指数（p<0.01），但只有 HFDCH 雄性小鼠使该参数恢复正常。回到标准饮食使 HFD 诱导的循环瘦素（p<0.001）、总 IGF1（p<0.001）、IGF2（p<0.001，仅在雌性）和 IGFBP3（p<0.001）升高恢复正常，而游离 IGF1 水平仍升高（p<0.01）。在雄性中，HFD 会降低 IGFBP2 并在标准饮食时恢复正常（p<0.001），而雌性没有变化。尽管恢复健康饮食可以改善分析的大多数代谢参数，但 fIGF1 水平仍然升高，并且下丘脑 ObR 在两种性别中均降低。此外，HFD 应答和切换到标准饮食包括循环 IGF2 和 IGFBP2 在内的性别差异，这些因素之前被报道与葡萄糖代谢有关。事实上，葡萄糖代谢在雄性和雌性中也有差异，这表明这些观察结果可能相关。
