Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL, USA.
Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, MA, USA.
J Nutr. 2022 Oct 6;152(10):2198-2208. doi: 10.1093/jn/nxac167.
Short-term starvation and severe food deprivation (FD) reduce dietary iron absorption and restricts iron to tissues, thereby limiting the amount of iron available for erythropoiesis. These effects may be mediated by increases in the iron regulatory hormone hepcidin; however, whether mild to moderate FD has similar effects on hepcidin and iron homeostasis is not known.
To determine the effects of varying magnitudes and durations of FD on hepcidin and indicators of iron status in male and female mice.
Male and female C57BL/6J mice (14 wk old; n = 170) were randomly assigned to consume AIN-93M diets ad libitum (AL) or varying magnitudes of FD (10%, 20%, 40%, 60%, 80%, or 100%). FD was based on the average amount of food consumed by the AL males or females, and food was split into morning and evening meals. Mice were euthanized at 48 h and 1, 2, and 3 wk, and hepcidin and indicators of iron status were measured. Data were analyzed by Pearson correlation and one-way ANOVA.
Liver hepcidin mRNA was positively correlated with the magnitude of FD at all time points (P < 0.05). At 3 wk, liver hepcidin mRNA increased 3-fold with 10% and 20% FD compared with AL and was positively associated with serum hepcidin (R = 0.627, P < 0.0001). Serum iron was reduced by ∼65% (P ≤ 0.01), and liver nonheme iron concentrations were ∼75% greater (P ≤ 0.01) with 10% and 20% FD for 3 wk compared with AL. Liver hepcidin mRNA at 3 wk was positively correlated with liver Bmp6 (R = 0.765, P < 0.0001) and liver gluconeogenic enzymes (R = >0.667, P < 0.05) but not markers of inflammation (P > 0.05).
FD increases hepcidin in male and female mice and results in hypoferremia and tissue iron sequestration. These findings suggest that increased hepcidin with FD may contribute to the disturbances in iron homeostasis with undernutrition.
短期饥饿和严重的食物剥夺（FD）会减少膳食铁的吸收，并将铁限制在组织中，从而限制用于红细胞生成的铁量。这些影响可能是由铁调节激素hepcidin 的增加介导的；然而，轻度至中度 FD 是否对 hepcidin 和铁稳态有类似的影响尚不清楚。
确定不同程度和持续时间的 FD 对雄性和雌性小鼠 hepcidin 和铁状态指标的影响。
将 14 周龄的雄性和雌性 C57BL/6J 小鼠（n = 170）随机分配为自由进食（AL）或不同程度的 FD（10%、20%、40%、60%、80%或 100%）。FD 是基于 AL 雄性或雌性消耗的平均食物量，并将食物分为早餐和晚餐。在 48 小时和 1、2 和 3 周时处死小鼠，并测量 hepcidin 和铁状态指标。通过 Pearson 相关和单因素方差分析进行数据分析。
肝 hepcidin mRNA 与各时间点 FD 的幅度呈正相关（P < 0.05）。在 3 周时，与 AL 相比，10%和 20% FD 使肝 hepcidin mRNA 增加 3 倍，且与血清 hepcidin 呈正相关（R = 0.627，P < 0.0001）。血清铁减少了约 65%（P ≤ 0.01），肝非血红素铁浓度增加了约 75%（P ≤ 0.01），与 AL 相比，3 周时的 10%和 20% FD。3 周时肝 hepcidin mRNA 与肝 Bmp6（R = 0.765，P < 0.0001）和肝糖异生酶（R > 0.667，P < 0.05）呈正相关，但与炎症标志物（P > 0.05）无关。
FD 增加雄性和雌性小鼠的 hepcidin，并导致低血症和组织铁蓄积。这些发现表明，FD 时 hepcidin 的增加可能导致营养不良时铁稳态的紊乱。
