Kao Alicia E, Moody Olivia P, Noble Emily E, Myers Kevin P, Kanoski Scott E, Hayes Anna M R
Department of Biological Sciences, Human and Evolutionary Biology Section, University of Southern California, 3616 Trousdale Parkway, AHF-252, Los Angeles, CA 90089-0372, USA.
Department of Foods and Nutrition, University of Georgia Athens, Athens, GA 30606, USA.
bioRxiv. 2025 Jun 25:2025.06.22.660913. doi: 10.1101/2025.06.22.660913.
Approximately 14% of U.S. households are estimated to be food insecure. The neurocognitive and metabolic impacts of unpredictable food access during early-life periods of development are poorly understood. To address these gaps we devised a novel rat model of food insecurity to control the timing, type, and quantity of accessible food using programmable feeders. Male rats were divided into 3 groups: Secure-chow (SC), a control group given 100% of daily caloric needs, distributed evenly across 4 daily meals of standard chow at set mealtimes; Secure-mixed (SM), a 2nd control group identical to the SC group except that the food type predictably alternated daily between chow and a high-fat, high-sugar diet (HFHS); and Insecure-mixed (IM), the experimental group given randomly alternating daily access to either chow or HFHS at either 85% or 115% of daily caloric needs, distributed evenly across 3 daily meals with unpredictable mealtimes. These feeding schedules were implemented from postnatal days (PNs) 26-45, after which all groups received chow ad libitum. Metabolic assessments performed in adulthood revealed no group differences in caloric intake, body weight, or body composition when maintained on either chow (PN46-149) or a cafeteria diet (PN150-174). Behavioral measures (PN66-126) revealed no group differences in anxiety-like, exploratory, or impulsive behavior (zero maze, open field, differential reinforcement of low rates of responding procedures). However, the IM group exhibited hippocampus-dependent memory impairments compared to both control groups in the novel location recognition test. These findings suggest that early-life food insecurity may contribute to long-term impairments in memory function.
据估计，美国约14%的家庭面临粮食不安全问题。人们对发育早期不可预测的食物获取对神经认知和代谢的影响了解甚少。为了填补这些空白，我们设计了一种新型的粮食不安全大鼠模型，使用可编程喂食器来控制可获取食物的时间、类型和数量。雄性大鼠被分为3组：安全饲料组（SC），作为对照组，给予每日热量需求的100%，在设定的用餐时间平均分配到4顿标准饲料餐中；安全混合组（SM），作为第二对照组，与SC组相同，只是食物类型每天可预测地在饲料和高脂肪、高糖饮食（HFHS）之间交替；不安全混合组（IM），作为实验组，每天随机交替获得饲料或HFHS，摄入量为每日热量需求的85%或115%，平均分配到3顿用餐中，用餐时间不可预测。这些喂食计划从出生后第26 - 45天开始实施，之后所有组自由进食饲料。成年后进行的代谢评估显示，当喂食饲料（出生后第46 - 149天）或自助餐饮食（出生后第150 - 174天）时，各组在热量摄入、体重或身体组成方面没有差异。行为测量（出生后第66 - 126天）显示，在焦虑样、探索性或冲动行为方面（零迷宫、旷场试验、低反应率差异强化程序）各组没有差异。然而，在新位置识别测试中，与两个对照组相比，IM组表现出海马体依赖的记忆损伤。这些发现表明，生命早期的粮食不安全可能导致记忆功能的长期损伤。
