Combined effects of high-fat diet feeding and Streptococcus agalactiae infection on lipid metabolism, antioxidant status, and immune response in tilapia (Oreochromis niloticus).

High-fat diet (HFD) and Streptococcus agalactiae are common pathogenic factors affecting tilapia health, yet their combined effects and underlying mechanisms are not well understood. To address this, we conducted a comprehensive evaluation of the potential response mechanisms in tilapia subjected to both factors. Tilapia were fed normal (NC) or high-fat diet (HFD) for 90 days, then challenged with S. agalactiae. At 48 h post-infection, blood, liver, and spleen samples were collected for biochemical parameter analysis and gene expression profiling. The results indicated that the combined treatment upregulated the expression of peroxisome proliferator-activated receptor α (pparα) and fatty acid transport protein 1 (fatp1). Concurrently, it increased 3-hydroxy-3-methylglutaryl-CoA reductase (hmgcr) expression, while decreasing cholesterol 7α-hydroxylase (cyp7a1) expression compared to HFD alone. Antioxidant status analysis revealed that the combined treatment decreased glutathione (GSH) content, total antioxidant capacity (T-AOC), and mRNA levels of nuclear factor erythroid 2-related factor 2 (nrf2), NAD(P)H quinone dehydrogenase 1 (nqo1), and glutathione peroxidase 3 (gpx3). Intriguingly, while both individual stressors upregulated inflammatory and immune-related genes, their combination suppressed interleukin-1β (il-1β), il-8, and immunoglobulin M (igm) expression compared to infection alone. The apoptotic response triggered by S. agalactiae infection, characterized by elevated caspase-3 (cas3), cas9, and cytochrome c (cytc), was inhibited in the liver of combined treatment group. Moreover, all experimental groups showed elevated expression of endoplasmic reticulum stress-related genes: inositol-requiring enzyme 1 (ire1), eukaryotic translation initiation factor 2 alpha kinase 3 (eif2ak3), activating transcription factor 6 (atf6), and binding immunoglobulin protein (bip). These findings collectively demonstrated that HFD exacerbated the pathogenic effects of S. agalactiae through multiple mechanisms, including metabolic dysregulation, oxidative stress potentiation, and complex immunomodulation. Furthermore, the Nrf2 and NF-kB signaling pathways may be implicated in mediating these adverse effects.