Betaine Alleviates LPS-Induced Chicken Skeletal Muscle Inflammation with the Epigenetic Modulation of the TLR4 Gene

SIMPLE SUMMARY: The poultry meat we eat is the skeletal muscle which comprises approximately three-quarters of the body weight of a chicken. In the modern poultry industry, the intensively raised broilers face the risk of exposure to environmental factors which can cause acute or chronic systemic inflammation. Inflammation, in return, contributes to the pathology of skeletal muscle diseases which are characterized by the loss of skeletal muscle mass. By adding betaine, a natural component, into the water of the newly hatched broilers for two weeks, we found that inflammation-related gene expression in the leg muscle was remarkably reduced. Specifically, we found that betaine inhibited the LPS-induced abnormal expression of IL-6 and TLR4. Further study indicated that the methylation modulation of the gene may be involved in betaine’s action. We suggest that betaine could be considered a safe and cheap preventive reagent candidate for chicken skeletal muscle inflammatory diseases. ABSTRACT: Betaine was found to alleviate inflammation in different studies. Here, newly hatched broilers were randomly divided into control and betaine consumptive groups, who had access to normal drinking water and water with betaine at a dose of 1000 mg/L, respectively. At the age of two weeks, the boilers were intraperitoneally treated with LPS. The protective effects of betaine against LPS-induced skeletal muscle inflammation were studied. Betaine attenuated the LPS-induced overexpression of IL-6 significantly in the leg muscle. Furthermore, LPS lowered the expression of TLR4 and TLR2 but increased the expression of MyD88. Betaine eliminated the effect of LPS on the expression of TLR4 but not TLR2 and MyD88. LPS also increased the expression of Tet methylcytosine dioxygenase 2 (Tet2), and this effect was also eliminated by betaine consumption. MeDIP-qPCR analysis showed that the methylation level in the promoter region of IL-6 was decreased by LPS treatment, whilst betaine cannot prevent this effect. On the contrary, LPS significantly increase the methylation level in the promoter region of TLR4, which was decreased by the consumption of betaine. Our findings suggest that betaine can alleviate LPS-induced muscle inflammation in chicken, and the regulation of aberrant DNA methylation might be a possible mechanism.