Division of Nephrology, Department of Medicine, and.
Department of Developmental Biology, Washington University in St. Louis, St. Louis, Missouri, USA.
J Clin Invest. 2024 Feb 15;134(4):e178125. doi: 10.1172/JCI178125.
Ten percent of the population worldwide suffers from chronic kidney disease (CKD), but the mechanisms driving CKD pathology are incompletely understood. While dysregulated lipid metabolism is one hallmark of CKD, the pathogenesis of cellular lipid accumulation remains unclear. In this issue of the JCI, Mukhi et al. Identify acyl-CoA synthetase short-chain family 2 (ACSS2) as a disease risk gene and demonstrate a role for ACSS2 in de novo lipogenesis (DNL). Notably, genetic or pharmacological inhibition of DNL protected against kidney disease progression in mice. These findings warrant evaluation of DNL inhibition with respect to efficacy and safety in people with CKD.
全球有 10%的人口患有慢性肾病（CKD），但导致 CKD 发病机制的原因还不完全清楚。尽管脂质代谢失调是 CKD 的一个标志特征，但细胞脂质积累的发病机制仍不清楚。在本期 JCI 中，Mukhi 等人将酰基辅酶 A 合成酶短链家族 2（ACSS2）鉴定为疾病风险基因，并证实 ACSS2 在从头合成脂肪（DNL）中发挥作用。值得注意的是，DNL 的遗传或药物抑制可防止小鼠的肾脏疾病进展。这些发现证明，在患有 CKD 的人群中，DNL 抑制的疗效和安全性值得进一步评估。
