Abstract
Background: Low dietary energy levels can disrupt energy balance, causing metabolic disorders, particularly those involving in hepatic lipid metabolism. Betaine (BET), an important methyl donor, has demonstrated protective effects against liver diseases. However, its effects on hepatic lipid metabolism in pigs fed a low-net energy (NE) diet and the underlying mechanisms remain unclear. Thirty-two pigs (85.52 ± 2.27 kg) were randomly assigned to four treatments: N-NE group (normal NE diet, 2,475 kcal/kg NE), N-NEB group (normal NE diet + 1,500 mg/kg BET, 2,475 kcal/kg NE), R100-NE group (low-NE diet, 2,375 kcal/kg NE), and R100-NEB group (low-NE diet + 1,500 mg/kg BET, 2,375 kcal/kg NE). The experiment lasted 35 d. Results: There was no significant difference in growth performance among the groups (P > 0.05). Reducing dietary NE levels caused liver dysfunction and increased total glyceride concentration, accompanied by lipid metabolism disorders. BET supplementation in a low-NE diet exhibited hepatoprotective roles, as evidenced by increased TP concentration and reduced ALT level in serum (P < 0.05), as well as decreased fat content, adipocyte size, and total glyceride concentration in the liver (P < 0.05). Meanwhile, dietary BET alleviated low-NE diet-induced hepatic lipid metabolism disorder by downregulating mRNA expressions of genes related to fatty acid transport (FABP3 and CD36) and lipogenesis (SREBP1c and FASN), while upregulating mRNA expressions involved in lipolysis (CPT1 and HSL) (P < 0.05). Furthermore, dietary BET increased serum SAM concentration and the SAM/SAH ratio in pigs fed low-NE diets (P < 0.05), thereby providing sufficient methyl groups through regulating the activities of enzymes participated in BET metabolism. Mechanistically, BET increased m6A modification level and regulated mRNA and protein expressions of m6A modified proteins including METTL3, METTL14, WTAP, YTHDF1, and ALKBH5. Correlation analysis showed a significant association between m6A RNA methylation and hepatic lipid metabolism, suggesting that m6A RNA methylation may play a critical role in mediating hepatic lipid metabolism. Conclusions: Dietary BET supplementation in low-NE diets alleviated hepatic lipid metabolism disorders by regulating m6A RNA methylation, ultimately reducing hepatic lipid accumulation in finishing pigs.