Betaine supplementation attenuates high-Se induced insulin resistance in C57BL/6 mice

Our previous research demonstrated that exogenous serine ameliorates insulin resistance in C57BL/6 mice fed a diet containing 0.8 mg/kg selenium, likely by serving as a methyl donor for SAM biosynthesis. This study aims to investigate whether betaine, an alternative methyl donor, can similarly mitigate high Se-induced IR in mice. Thirty C57BL/6 mice were randomized into three groups fed: (1) 0.1 mg/kg Se (non-IR control group), (2) 0.8 mg/kg Se (IR control group), and (3) 0.8 mg/kg Se with Bet supplementation (IR+Bet intervention group). The experiment was conducted in two phases: a 4-month period of IR induction via high-Se diet, followed by a 1-month Bet intervention period. Plasma Se, insulin, and fasting glucose levels were assessed at baseline, and both before and after Bet intervention. Plasma homocysteine, lipid profiles (HDL, LDL, TCHO, TG), as well as glucose tolerance tests and insulin tolerance tests, were measured before and after intervention. After euthanasia, Se content, selenoprotein levels, and the expression of enzymes related to Ser synthesis and metabolism were measured in various tissues. After 1 month of Bet supplementation, mice in the IR+Bet intervention group exhibited significantly higher insulin sensitivity in ITT (P<.01), and lower expression of PHGDH in liver, skeletal muscle, and pancreas tissues (P<.05), compared to the IR control group. Additionally, plasma lipid profiles were significantly improved in the IR+Bet intervention group (P<.05). This is the first report demonstrating that Bet supplementation, like exogenous Ser, can effectively improve hyperglycemia and insulin resistance in mice fed a high-Se diet.