Department of Genetics, Physiology and Microbiology, Faculty of Biology, Complutense University of Madrid and Research Institute of Hospital 12 de Octubre (i+12), Spain.
Department of Genetics, Physiology and Microbiology, Faculty of Biology, Complutense University of Madrid and Research Institute of Hospital 12 de Octubre (i+12), Spain.
Brain Behav Immun. 2019 May;78:65-77. doi: 10.1016/j.bbi.2019.01.010. Epub 2019 Jan 16.
The aim of the present study was to investigate whether the late onset of diet-induced obesity (DIO) in middle-aged mice affected behavioral, immunological and oxidative stress parameters as well as life span of male and female mice. Also, it was analyzed whether the late DIO onset aggravated immunosenescence in old female mice. Late-adult male and female ICR/CD1 mice (28 weeks old) were fed either a high-fat diet or a standard diet during 14 weeks. After that, in these middle-aged (42 weeks old) diet-induced obese (DIO) and non-DIO controls, behavior as well as functions and redox state of peritoneal leukocytes were evaluated. These same parameters (excepting behavioral tests) were repeated when female mice were old (72 weeks old). The results showed lower exploratory activity and higher anxiety-like behavior in middle-aged male and female DIO than in controls. Moreover, these DIO animals from both sexes exhibited statistically significant impaired immune cell functions, such as chemotaxis of macrophages and lymphocytes, phagocytosis of macrophages, natural killer activity and lymphoproliferation in response to ConA and LPS, as well as an oxidative stress state in comparison with controls. Male DIO mice exhibited higher impairments in a variety of the evaluated parameters and a shorter life span than their female counterparts. In addition, female DIO mice, at old age, showed aggravated immunosenescence. In conclusion, the late DIO onset leads to impairments in behavior as well as in immune system functions of middle-aged male and female mice, males being significantly more affected than females.
本研究旨在探讨中年小鼠的饮食诱导肥胖(DIO)晚期发作是否会影响雄性和雌性小鼠的行为、免疫和氧化应激参数以及寿命。此外,还分析了晚期 DIO 发作是否会加剧老年雌性小鼠的免疫衰老。将雄性和雌性 ICR/CD1 小鼠(28 周龄)分为两组,分别给予高脂肪饮食或标准饮食喂养 14 周。之后,对这些中年(42 周龄)饮食诱导肥胖(DIO)和非 DIO 对照组小鼠进行行为以及腹腔白细胞功能和氧化还原状态评估。当雌性小鼠进入老年(72 周龄)时,重复这些相同的参数(除行为测试外)。结果表明,与对照组相比,中年雄性和雌性 DIO 小鼠的探索性活动减少,焦虑样行为增加。此外,与对照组相比,这些来自不同性别的 DIO 动物的免疫细胞功能显著受损,如巨噬细胞和淋巴细胞的趋化性、巨噬细胞的吞噬作用、NK 细胞活性和 ConA 和 LPS 刺激的淋巴细胞增殖,以及氧化应激状态。雄性 DIO 小鼠在多种评估参数上的损伤程度高于雌性,寿命也短于雌性。此外,老年雌性 DIO 小鼠表现出更严重的免疫衰老。总之,晚期 DIO 发作会导致中年雄性和雌性小鼠的行为以及免疫系统功能受损,雄性比雌性受影响更严重。