miR-143-Mediated Responses to Betaine Supplement Repress Lipogenesis and Hepatic Gluconeogenesis by Targeting MAT1a and MAPK11

甜菜碱 脂肪生成 糖异生 脂质代谢 生物 新陈代谢 脂解 碳水化合物代谢 脂肪肝 生物化学 葡萄糖稳态 内分泌学 化学 内科学 胰岛素抵抗 胰岛素 脂肪组织 医学 疾病
作者
Xingping Chen,Junyi Luo,Lekai Yang,Yue Leon Guo,Yaotian Fan,Jie Liu,Jiajie Sun,Yongliang Zhang,Qingyan Jiang,Ting Chen,Qianyun Xi
出处
期刊:Journal of Agricultural and Food Chemistry [American Chemical Society]
卷期号:70 (26): 7981-7992 被引量:12
标识
DOI:10.1021/acs.jafc.2c02940
摘要

The liver as the central organ is responsible for lipogenesis, gluconeogenesis and one-carbon metabolism. Methyl donors (e.g., betaine) modulate metabolic homeostasis and gene regulation through one-carbon metabolism. MiR-143 regulates DNA methylation by targeting DNMT3A, thereby suggesting that this miRNA participates in one-carbon metabolic pathways. However, the effect and mechanism that regulate glucose and lipid metabolism via the methyl group metabolism pathway remain elusive. In this study, we found that a betaine supplement and miR-143 KO significantly promoted lipolysis and glucose utilization and repressed lipogenesis and gluconeogenesis through enhancing energy consumption and thermogenesis, repressing GPNMB and targeting MAPK11, respectively. We further explored the relationship between miR-143 and a methyl donor (betaine) and the miR-143-mediated responses to the betaine supplement regulating the mechanism of the glucose and lipid metabolism. The results showed that betaine significantly down-regulated the expression of miR-143 that subsequently increased SAM levels in the liver by targeting MAT1a. In brief, the regulations of glucose and lipid metabolism are related to the miR-143-regulation of one-carbon units, and the relationship between betaine and miR-143 in the methionine cycle is a typical yin-yang type of regulation. Thus, betaine and miR-143 function together as key regulators and biomarkers for preventing and diagnosing metabolic diseases such as fatty liver disease, obesity, and diabetes.
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