Kathirvel Elango, Morgan Kengathevy, Malysheva Olga V, Caudill Marie A, Morgan Timothy R
Research Healthcare Group, Veterans Administration Healthcare System, Long Beach, CA, United States.
Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
Front Nutr. 2024 Jul 25;11:1409972. doi: 10.3389/fnut.2024.1409972. eCollection 2024.
The aim was to investigate mechanisms by which betaine improves hepatic insulin signaling in a dietary mouse model of insulin resistance and fatty liver.
C57BL 6J mice were fed a standard diet (SF), a standard diet with betaine (SFB), a nutritionally complete high fat (HF) diet, or a high fat diet with betaine (HFB) for 14 weeks. In a separate experiment, mice were fed high fat diet for 18 weeks, half of whom received betaine for the final 4 weeks. Activation of insulin signaling in the liver was assessed by western blot. Insulin signaling was also assessed in insulin resistant primary human hepatocytes treated with betaine.
As compared with SF, mice receiving HF diet were heavier, had more hepatic steatosis, and abnormal glucose tolerance test (GTT). Betaine content in liver and serum was 50% lower in HF than in SF; betaine supplementation restored serum and liver betaine content. Betaine treatment of HF reduced whole body insulin resistance as measured by GTT. Betaine treatment of HF increased tyrosine phosphorylation of insulin receptor substrate-1 and phosphorylation (activation) of Akt, and increased hepatic glycogen content. , betaine reversed insulin resistance in primary human hepatocytes by increasing insulin-stimulated tyrosine phosphorylation of IRS1 and of Akt.
Betaine supplementation reduced whole body insulin resistance and increased activation of insulin signaling pathways in the liver in a mouse model of insulin resistance and fatty liver created by feeding a nutritionally complete high fat diet for 14 weeks. Betaine also reduced liver injury as assessed by ALT and by liver histology. , betaine reversed insulin resistance by increasing insulin-stimulated tyrosine phosphorylation of IRS1 and activation of downstream proteins in the insulin signaling cascade in insulin resistant primary human hepatocytes.
本研究旨在探讨在胰岛素抵抗和脂肪肝饮食小鼠模型中，甜菜碱改善肝脏胰岛素信号传导的机制。
将C57BL 6J小鼠分为四组，分别喂食标准饮食（SF）、添加甜菜碱的标准饮食（SFB）、营养完全的高脂肪饮食（HF）或添加甜菜碱的高脂肪饮食（HFB），持续14周。在另一项实验中，小鼠先喂食高脂肪饮食18周，其中一半在最后4周给予甜菜碱。通过蛋白质免疫印迹法评估肝脏中胰岛素信号的激活情况。同时也在经甜菜碱处理的胰岛素抵抗原代人肝细胞中评估胰岛素信号。
与SF组相比，接受HF饮食的小鼠体重更重，肝脂肪变性更严重，葡萄糖耐量试验（GTT）异常。HF组肝脏和血清中的甜菜碱含量比SF组低50%；补充甜菜碱可恢复血清和肝脏中的甜菜碱含量。用甜菜碱处理HF组可降低通过GTT测量的全身胰岛素抵抗。用甜菜碱处理HF组可增加胰岛素受体底物-1的酪氨酸磷酸化和Akt的磷酸化（激活），并增加肝糖原含量。此外，甜菜碱通过增加胰岛素刺激的IRS1酪氨酸磷酸化和Akt磷酸化，逆转了原代人肝细胞中的胰岛素抵抗。
在通过喂食营养完全的高脂肪饮食14周建立的胰岛素抵抗和脂肪肝小鼠模型中，补充甜菜碱可降低全身胰岛素抵抗，并增加肝脏中胰岛素信号通路的激活。甜菜碱还可降低通过谷丙转氨酶（ALT）和肝脏组织学评估的肝损伤。此外，甜菜碱通过增加胰岛素刺激的IRS1酪氨酸磷酸化和胰岛素抵抗原代人肝细胞中胰岛素信号级联下游蛋白的激活，逆转了胰岛素抵抗。
