Adult Zucker Obese fa/fa Rats Present Impaired Immunity and Oxidative-Inflammatory Responses

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first_pagesettingsOrder Article Reprints Open AccessArticle Adult Zucker Obese fa/fa Rats Present Impaired Immunity and Oxidative-Inflammatory Responses by Nuria María De Castro 1,2,*ORCID,Mónica De la Fuente 3,4ORCID,Lydia Giménez-Llort 5,6ORCID,Jaime Ruiz-Tovar 7ORCID,Carmen Vida 8,9ORCID andMaría Isabel Baeza 1,2ORCID 1 Health Sciences Department, San Juan de Dios School of Nursing and Physical Therapy, Comillas Pontifical University, 28036 Madrid, Spain 2 San Juan de Dios Foundation, 28036 Madrid, Spain 3 Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Complutense University of Madrid, 28040 Madrid, Spain 4 Institute of Investigation 12 de Octubre Hospital (Imas12), 28041 Madrid, Spain 5 Department of Psychiatry and Forensic Medicine, School of Medicine, Autonomous University of Barcelona, 08193 Barcelona, Spain 6 Institute of Neuroscience (INc), Autonomous University of Barcelona, 08193 Barcelona, Spain 7 Department of Biomedicine and Health Sciences, Alfonso X University, 28691 Madrid, Spain 8 Department of Biology (Animal Physiology Area), Faculty of Sciences, Autonomous University of Madrid, 28049 Madrid, Spain 9 University Institute of Molecular Biology (IUBM), Autonomous University of Madrid, 28049 Madrid, Spain * Author to whom correspondence should be addressed. Biomolecules 2026, 16(4), 547; https://doi.org/10.3390/biom16040547 Submission received: 25 February 2026 / Revised: 25 March 2026 / Accepted: 31 March 2026 / Published: 8 April 2026 (This article belongs to the Special Issue Oxidative Stress and Inflammation in Aging and Cancer: Biological Bases, Therapeutic Strategies and Opportunities) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract Background: Obesity involves an excessive buildup of adipose tissue and is linked to chronic inflammation and oxidative stress, both of which contribute to immunosenescence. Obesity and aging share common features, including immune system impairment and oxidative and inflammatory states, suggesting that obesity may represent a model for accelerated immunosenescence. Objectives/Methods: The aim of this research was to evaluate in Zucker fatty (fa/fa) rats, a well-established genetic model of obesity, multiple immune function parameters (phagocytic activity, natural killer cell function, lymphocyte proliferation in response to mitogens, and cytokine profiles), as well as redox parameters (total antioxidant capacity, glutathione levels, activities of glutathione peroxidase and reductase, and xanthine oxidase activity) in peritoneal leukocytes, spleen, thymus, and liver at adult age (24 weeks). Comparisons were made with Zucker lean controls (fa/+), commonly used as standard controls, and Wistar rats as an independent control group. Results: Zucker fa/fa rats displayed significant physiological disorders, including increased body and organ weights, premature immunosenescence characterized by impaired innate and adaptive immune responses, reduced IL-2 and IL-10 secretion, elevated TNF-α production upon mitogen stimulation, and oxidative stress evidenced by redox imbalance in the spleen, thymus, and liver. Conclusions: These immune dysfunctions and oxidative imbalances are comparable to those observed during the aging process. Given that the immune parameters analyzed are considered indicators of health, aging rate, and longevity, our findings suggest that adult Zucker fa/fa rats could exhibit features of premature aging.