High-fat overfeeding is associated with tissue-specific liver-adipose immunometabolic remodeling in rainbow trout

The excessive accumulation of visceral adipose tissue is associated with ectopic lipid deposition, impairing the function of major metabolic organs, including the liver, and contributing to systemic inflammatory responses. In aquaculture, farmed fish have limited capacity to autonomously regulate feed intake, as caloric intake is largely determined by feeding practices, predisposing them to excessive energy consumption and metabolic imbalance. This study investigated how excessive feeding affects metabolic and immune responses in the liver and adipose tissue of rainbow trout and whether these alterations increase susceptibility to infection. A total of 195 rainbow trout were assigned to three feeding regimes: normal feeding with an 8% fat diet (NF8), normal feeding with a 22% fat diet (NF22), and overfeeding with a 22% fat diet (OF22). Fish were fed for 12 weeks and sampled at 2, 4, 8, and 12 weeks to assess growth performance, serological parameters, immune responses, and pathogen susceptibility. RNA sequencing-based transcriptomic analysis was conducted on liver samples at weeks 2 and 8 and on adipose tissue samples at weeks 2, 4, and 8. Fish in the OF22 group exhibited significantly increased body weight, body mass index, and serum aspartate aminotransferase, alanine aminotransferase, and triglyceride levels compared to the other groups, accompanied by adipocyte hypertrophy. Transcriptomic analysis revealed the upregulation of fatty acid biosynthesis and oxidative phosphorylation pathways in the liver, and the downregulation of immune-related pathways, including complement and coagulation cascades. In contrast, adipose tissue showed enhanced lipid and energy metabolism, elevated expression of pro-inflammatory markers (interleukin (il)-1β, il-6, tumor necrosis factor-α, and inducible nitric oxide synthase), reduced anti-inflammatory and M2 macrophage-associated markers (il-10 and cd163), and the sustained activation of complement-related pathways. These tissue-specific immunometabolic changes were linked to a higher susceptibility to Aeromonas salmonicida infection and increased mortality after the challenge. Overall, the study results show that the OF22 condition was associated with tissue-specific immunometabolic imbalance in farmed fish, leading to metabolic disturbances and weakened immune responses.