Department of Nutrition & Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Department of Nutrition & Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Pharmacol Res. 2019 Jun;144:116-131. doi: 10.1016/j.phrs.2019.04.002. Epub 2019 Apr 5.
In the past two decades, significant advances have been made in the etiology of lipid disorders. Concomitantly, the discovery of liporegulatory functions of certain short-chain fatty acids has generated interest in their clinical applications. In particular, butyric acid (BA) and its derivative, 4-phenylbutyric acid (PBA), which afford health benefits against lipid disorders while being generally well tolerated by animals and humans have been assessed clinically. This review examines the evidence from cell, animal and human studies pertaining to the lipid-regulating effects of BA and PBA, their molecular mechanisms and therapeutic potential. Collectively, the evidence supports the view that intakes of BA and PBA benefit lipid homeostasis across biological systems. We reviewed the evidence that BA and PBA downregulate de novo lipogenesis, ameliorate lipotoxicity, slow down atherosclerosis progression, and stimulate fatty acid β-oxidation. Central to their mode of action, BA appears to function as a histone deacetylase (HDAC) inhibitor while PBA acts as a chemical chaperone and/or a HDAC inhibitor. Areas of further inquiry include the effects of BA and PBA on adipogenesis, lipolysis and apolipoprotein metabolism.
在过去的二十年中，脂质代谢紊乱的病因学取得了重大进展。同时，某些短链脂肪酸的脂调节功能的发现引起了人们对其临床应用的兴趣。特别是丁酸（BA）及其衍生物 4-苯基丁酸（PBA），在动物和人体中具有良好的耐受性的同时，对脂质代谢紊乱具有有益作用，已在临床上进行了评估。这篇综述检查了细胞、动物和人体研究中关于 BA 和 PBA 的脂质调节作用、它们的分子机制和治疗潜力的证据。总的来说，这些证据支持这样一种观点，即摄入 BA 和 PBA 有益于整个生物系统的脂质动态平衡。我们回顾了 BA 和 PBA 下调从头合成脂质、改善脂毒性、减缓动脉粥样硬化进展和刺激脂肪酸β氧化的证据。BA 似乎作为组蛋白去乙酰化酶（HDAC）抑制剂发挥作用，而 PBA 作为化学伴侣和/或 HDAC 抑制剂发挥作用，这是其作用模式的核心。进一步研究的领域包括 BA 和 PBA 对脂肪生成、脂肪分解和载脂蛋白代谢的影响。
