Kameno Koki, Hasegawa Yu, Hayashi Kenyu, Takemoto Yushin, Uchikawa Hiroki, Mukasa Akitake, Kim-Mitsuyama Shokei
Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Japan.
Department of Pharmaceutical Science, School of Pharmacy at Fukuoka, International University of Health and Welfare, Japan.
Exp Gerontol. 2022 Sep;166:111885. doi: 10.1016/j.exger.2022.111885. Epub 2022 Jul 2.
The cause of age-related body weight loss in Alzheimer's disease (AD) is unclear. We compared the differences in food intake, malabsorption, locomotor activity, and gut microbiota composition between 5xFAD mice, a useful model of AD, and wild-type (WT) mice to investigate the mechanisms underlying lower body weight in 5xFAD mice. Fifteen-month-old male 5xFAD mice and age-matched WT mice were divided into four groups: a control diet (CD) or a high-fat diet (HFD). After feeding CD or HFD for eight to nine weeks, 5xFAD mice had a significantly lower body weight than WT mice regardless of diet (p < 0.05). Additionally, the 5xFAD mice did not show a reduction in food intake compared to the WT mice regardless of diet. To evaluate malabsorption, we performed a fecal fat test. There was no obvious fecal fat in both the 5xFAD mice and WT mice. However, 5xFAD mice showed greater locomotor activity than WT mice in the Y-maze test. The comprehensive analysis of gut microbiota composition showed that 15-month-old 5xFAD mice had more Proteobacteria population and fewer Actinobacteria and Bifidobacteriales populations than WT mice. To investigate the effects of fructooligosaccharides (FOS), we administrated FOS to 15-month-old 5xFAD mice. FOS administration decreased Proteobacteria and increased Actinobacteria population, although that did not change Bifidobacteriales population. Moreover, cognitive impairment and body weight of 5xFAD mice were not changed by FOS administration. In conclusion, loss of body weight in 15-month-old 5xFAD mice might be partially derived from excess energy output by hyperactivity. Moreover, 15-month-old 5xFAD mice might have unique alteration of gut microbiota composition and the potential resistance to FOS.
阿尔茨海默病（AD）中与年龄相关的体重减轻原因尚不清楚。我们比较了5xFAD小鼠（一种有用的AD模型）和野生型（WT）小鼠在食物摄入量、吸收不良、运动活动和肠道微生物群组成方面的差异，以研究5xFAD小鼠体重较低的潜在机制。将15个月大的雄性5xFAD小鼠和年龄匹配的WT小鼠分为四组：对照组饮食（CD）或高脂饮食（HFD）。在给予CD或HFD八至九周后，无论饮食如何，5xFAD小鼠的体重均显著低于WT小鼠（p < 0.05）。此外，无论饮食如何，与WT小鼠相比，5xFAD小鼠的食物摄入量均未减少。为了评估吸收不良情况，我们进行了粪便脂肪测试。5xFAD小鼠和WT小鼠的粪便中均未发现明显的脂肪。然而，在Y迷宫测试中，5xFAD小鼠比WT小鼠表现出更大的运动活动。肠道微生物群组成的综合分析表明，15个月大的5xFAD小鼠的变形菌门菌群比WT小鼠更多，而放线菌门和双歧杆菌目菌群比WT小鼠更少。为了研究低聚果糖（FOS）的作用，我们给15个月大的5xFAD小鼠施用了FOS。施用FOS后，变形菌门减少，放线菌门增加，尽管双歧杆菌目菌群没有变化。此外，施用FOS并未改变5xFAD小鼠的认知障碍和体重。总之，15个月大的5xFAD小鼠体重减轻可能部分源于多动导致的能量输出过多。此外，1个月大的5xFAD小鼠可能具有独特的肠道微生物群组成变化以及对FOS的潜在抗性。
