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
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