L-theanine regulates the immune function of SD rats fed high-protein diets through the FABP5/IL-6/STAT3/PPARα pathway.

The protein levels in a diet are correlated with immunity but the long-term intake of excessive protein can compromise various aspects of health. L-theanine regulates immunity and protein metabolism; however, how its regulatory immunity effects under a high-protein diet are unclear. We used proteomics, metabonomics, and western blotting to analyze the effects of diets with different protein levels on immune function in rats to determine the role of L-theanine in immunity under a high-protein diet. The long-term intake of high-protein diets (≥40% protein) promoted oxidative imbalance and inflammation. These were alleviated by L-theanine. High-protein diets inhibited peroxisome proliferator-activated receptor (PPAR)α expression through the interleukin (IL)-6/signal transducer and activator of transcription (STAT)3 pathway and mediated inflammation. L-theanine downregulated anti-fatty acid-binding protein 5 (FABP5), inhibited the IL-6/STAT3 axis, and reduced high-protein diet-induced PPARα inhibition. Therefore, L-theanine alleviates the adverse effects of high-protein diets via the FABP5/IL-6/STAT3/PPARα pathway and regulates the immunity of normally fed rats through the epoxide hydrolase (EPHX)2/nuclear factor-kappa B inhibitor (IκB)α/triggering receptor expressed on myeloid cells (TREM)1 axis.