College of Animal Sciences, Zhejiang University, Hangzhou, China; Laboratory of Molecular Animal Nutrition, Zhejiang University, Ministry of Education, Hangzhou, China; Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, China; Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Hangzhou, China.
College of Animal Sciences, Zhejiang University, Hangzhou, China; Laboratory of Molecular Animal Nutrition, Zhejiang University, Ministry of Education, Hangzhou, China; Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Hangzhou, China; Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Hangzhou, China.
J Nutr Biochem. 2024 Dec;134:109738. doi: 10.1016/j.jnutbio.2024.109738. Epub 2024 Aug 21.
Nonalcoholic fatty liver disease (NAFLD) has emerged as a major public health crisis with significant health threats and economic burdens worldwide in the past decades. Betaine, a naturally occurring alkaloid compound present in various dietary sources including spinach and beets, has been shown to ameliorate hepatic lipid metabolism and attenuate (NAFLD), while the underlying mechanism remains elusive. Here, we propose a novel mechanism through which betaine exerts its protective effects against hepatic lipid accumulation and (NAFLD) from an epigenetics perspective. Specifically, we discover that betaine upregulates betaine homocysteine S-methyltransferase (BHMT) expression, leading to increased nicotinamide adenine dinucleotide phosphate (NADPH) production and subsequent upregulation of fat mass and obesity-associated protein (FTO) expression. Increased abundance of FTO targets peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1α) mRNA and reduces the N-methyladenosine (mA) level in the CDS of Ppargc1α transcript, which positively regulates PGC1α expression and subsequently inhibits hepatic lipid accumulation. Overall, our works demonstrate that betaine may be a promising therapeutic strategy for treating (NAFLD) and improving liver function through the regulation of (NADPH) and mA-mediated pathways.
非酒精性脂肪性肝病（NAFLD）在过去几十年中已成为全球范围内主要的公共卫生危机，对健康构成重大威胁，并带来了巨大的经济负担。甜菜碱是一种天然存在的生物碱化合物，存在于各种饮食来源中，如菠菜和甜菜，已被证明可以改善肝脏的脂质代谢并减轻（NAFLD），但其潜在机制尚不清楚。在这里，我们从表观遗传学的角度提出了一种新的机制，即甜菜碱通过该机制发挥其对肝脏脂质积累和（NAFLD）的保护作用。具体来说，我们发现甜菜碱上调甜菜碱同型半胱氨酸 S-甲基转移酶（BHMT）的表达，导致烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的产生增加，随后脂肪质量和肥胖相关蛋白（FTO）的表达上调。FTO 的丰度增加会导致过氧化物酶体增殖物激活受体-γ共激活因子 1-α（PGC1α）mRNA 的靶标增加，并降低 Ppargc1α 转录物 CDS 中的 N6-甲基腺苷（mA）水平，这正向调节 PGC1α 的表达，随后抑制肝脏脂质积累。总的来说，我们的研究表明，甜菜碱可能是一种有前途的治疗策略，可通过调节（NADPH）和 mA 介导的途径治疗（NAFLD）并改善肝功能。
