High-fat diet blunts T-cell responsiveness in Nile tilapia.

The reduced stress resistance and increased disease risk associated with high-fat diet (HFD) in animals have attracted increasing attention. However, the effects of HFD on adaptive immunity in early vertebrates, especially non-tetrapods, remain unknown. In this study, using Nile tilapia (Oreochromis niloticus) as a model, we investigated the effects of HFD on the primordial T-cell response in fish. Tilapia fed with an HFD for 8 weeks showed impaired lymphocyte homeostasis in the spleen, as indicated by the decreased number of both T and B lymphocytes and increased transcription of proinflammatory cytokines interferon-γ and interleukin-6. Moreover, lymphocytes isolated from HFD-fed fish or cultured in lipid-supplemented medium exhibited diminished T-cell activation in response to CD3ε monoclonal antibody stimulation. Moreover, HFD-fed tilapia infected by Aeromonas hydrophila showed decreased T-cell expansion, increased T-cell apoptosis, reduced granzyme B expression, and impaired infection elimination. Additionally, HFD attenuated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activity in tilapia lymphocytes, which in turn upregulated fatty acid synthesis but downregulated fatty acid β-oxidation. Altogether, our results suggest that HFD impairs lymphocyte homeostasis and T cell-mediated adaptive immune response in tilapia, which may be associated with the abnormal lipid metabolism in lymphocytes. These findings thus provide a novel perspective for understanding the impact of HFD on the adaptive immune response of early vertebrates.