甜菜碱通过涉及 BHMT/FTO/m6A/ PGC1α 信号传导的方式缓解非酒精性脂肪肝(NAFLD)。

IF 4.8 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Nutritional Biochemistry Pub Date : 2024-08-21 DOI:10.1016/j.jnutbio.2024.109738
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引用次数: 0

摘要

非酒精性脂肪肝(NAFLD)在过去几十年中已成为一个重大的公共卫生危机,在全球范围内造成了严重的健康威胁和经济负担。甜菜碱是一种天然生物碱化合物,存在于包括菠菜和甜菜在内的多种膳食来源中,已被证明可改善肝脏脂质代谢和减轻非酒精性脂肪肝,但其潜在机制仍难以捉摸。在这里,我们从表观遗传学的角度提出了甜菜碱对肝脏脂质积累和非酒精性脂肪肝产生保护作用的新机制。具体来说,我们发现甜菜碱能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酯(NADPH)生成增加,进而上调脂肪量和肥胖相关蛋白(FTO)的表达。FTO 丰度的增加以过氧化物酶体增殖激活受体-γ 辅激活剂 1-α(PGC1α)mRNA 为靶标,并降低 Ppargc1α 转录本 CDS 中的 N6-甲基腺苷(m6A)水平,从而正向调节 PGC1α 的表达,进而抑制肝脏脂质积累。总之,我们的研究结果表明,甜菜碱可通过调节NADPH和m6A介导的途径治疗非酒精性脂肪肝,并改善肝功能。
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Betaine alleviates nonalcoholic fatty liver disease (NAFLD) via a manner involving BHMT/FTO/m6A/ PGC1α signaling

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 N6-methyladenosine (m6A) 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 m6A-mediated pathways.

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来源期刊
Journal of Nutritional Biochemistry
Journal of Nutritional Biochemistry 医学-生化与分子生物学
CiteScore
9.50
自引率
3.60%
发文量
237
审稿时长
68 days
期刊介绍: Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology. Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.
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