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.

中文翻译：

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丁酸和4-苯基丁酸的脂质调节特性：分子机理和治疗应用。

在过去的二十年中，脂质疾病的病因学已取得重大进展。伴随地，某些短链脂肪酸的脂调节功能的发现引起了对其临床应用的兴趣。尤其是，已经对临床上评估了丁酸（BA）及其衍生物4-苯基丁酸（PBA）产生了抗脂质紊乱的健康益处，同时通常被动物和人类很好地耐受。这篇综述检查了来自细胞，动物和人体研究的证据，这些证据与BA和PBA的脂质调节作用，它们的分子机制和治疗潜力有关。总的来说，证据支持这样的观点，即BA和PBA的摄入有益于整个生物系统的脂质稳态。我们审查了BA和PBA下调新生脂肪形成的证据，改善脂质毒性，减缓动脉粥样硬化的发展，并刺激脂肪酸β-氧化。在其作用方式中，BA似乎起着组蛋白脱乙酰基酶（HDAC）抑制剂的作用，而PBA则起着化学伴侣和/或HDAC抑制剂的作用。进一步研究的领域包括BA和PBA对脂肪生成，脂解和载脂蛋白代谢的影响。