Department of Food & Nutrition, Obesity/Diabetes Center, Hoseo University, Asan 336-795, South Korea.
Exp Biol Med (Maywood). 2018 Feb;243(4):334-343. doi: 10.1177/1535370217751610. Epub 2018 Jan 7.
Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused with β-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared to the Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly, cortisol levels were increased by Alzheimer's disease but decreased by intermittent fasting. Intermittent fasting improved dyslipidemia and liver damage index compared to ad libitum. Alzheimer's disease lowered low-density lipoprotein cholesterol and serum triglyceride levels compared to Non-Alzheimer's disease. In conclusion, Alzheimer's disease impaired not only cognitive function but also disturbed energy, glucose, lipid, and bone metabolism in ovariectomized rats. Intermittent fasting protected against the deterioration of these metabolic parameters, but it exacerbated bone mineral density loss and insulin resistance at fasting in Alzheimer's disease-induced estrogen-deficient rats. Impact statement Intermittent fasting was evaluated for its effects on cognitive function and metabolic disturbances in a rat model of menopause and Alzheimer's disease. Intermittent fasting decreased skin temperature and fat mass, and improved glucose tolerance with decreasing food intake. Intermittent fasting also prevented memory loss: short-term and special memory loss. Therefore, intermittent fasting may prevent some of the metabolic pathologies associated with menopause and protect against age-related memory decline.
间歇性禁食可能是一种有效的干预措施，可以预防与年龄相关的代谢紊乱，尽管它仍存在争议。在这里，我们研究了间歇性禁食对去卵巢大鼠代谢和认知功能恶化的影响，并探讨了其机制。β-淀粉样蛋白（25-35；阿尔茨海默病）或β-淀粉样蛋白（35-25，非阿尔茨海默病；正常认知功能）被输注到海马体中的去卵巢大鼠。每个组被随机分为两个亚组：一组进行间歇性禁食，另一组自由进食：阿尔茨海默病-自由进食、阿尔茨海默病-间歇性禁食、非阿尔茨海默病-自由进食和非阿尔茨海默病-间歇性禁食。间歇性禁食组的大鼠每天将食物摄入量限制在 3 小时内。每个组包括 10 只大鼠，所有大鼠均喂食高脂肪饮食 4 周。有趣的是，与非阿尔茨海默病相比，阿尔茨海默病大鼠的尾巴皮肤温度升高更多，而间歇性禁食可预防这种升高。与非阿尔茨海默病相比，阿尔茨海默病大鼠的脊柱和股骨骨密度降低，而髋部和腿部的骨密度则因间歇性禁食而降低。仅腹部的脂肪量减少。间歇性禁食减少了食物摄入，而不改变能量消耗。阿尔茨海默病增加了葡萄糖氧化，而间歇性禁食增加了脂肪氧化作为燃料来源。与非阿尔茨海默病相比，阿尔茨海默病和间歇性禁食在禁食状态下降低了胰岛素敏感性，但间歇性禁食通过增加胰岛素分泌来降低口服葡萄糖后血清葡萄糖水平。与自由进食相比，阿尔茨海默病大鼠的短期和空间记忆功能恶化，而间歇性禁食可预防记忆丧失。出乎意料的是，皮质醇水平因阿尔茨海默病而升高，但因间歇性禁食而降低。与自由进食相比，间歇性禁食改善了血脂异常和肝损伤指数。与非阿尔茨海默病相比，阿尔茨海默病降低了低密度脂蛋白胆固醇和血清甘油三酯水平。总之，阿尔茨海默病不仅损害了认知功能，还破坏了去卵巢大鼠的能量、葡萄糖、脂质和骨骼代谢。间歇性禁食可防止这些代谢参数恶化，但在阿尔茨海默病诱导的去卵巢大鼠中，它会加剧空腹时的骨密度丢失和胰岛素抵抗。影响描述 间歇性禁食在绝经和阿尔茨海默病的大鼠模型中被评估了其对认知功能和代谢紊乱的影响。间歇性禁食降低了皮肤温度和脂肪量，并通过减少食物摄入改善了葡萄糖耐量。间歇性禁食还防止了记忆丧失：短期和特殊记忆丧失。因此，间歇性禁食可能预防与绝经相关的一些代谢病理学，并防止与年龄相关的记忆衰退。
