Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, Utah, USA; email:
Diabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, Utah, USA.
Annu Rev Nutr. 2022 Aug 22;42:115-144. doi: 10.1146/annurev-nutr-062220-112920. Epub 2022 May 18.
Diet influences onset, progression, and severity of several chronic diseases, including heart failure, diabetes, steatohepatitis, and a subset of cancers. The prevalence and clinical burden of these obesity-linked diseases has risen over the past two decades. These metabolic disorders are driven by ectopic lipid deposition in tissues not suited for fat storage, leading to lipotoxic disruption of cell function and survival. Sphingolipids such as ceramides are among the most deleterious and bioactive metabolites that accrue, as they participate in selective insulin resistance, dyslipidemia, oxidative stress and apoptosis. This review discusses our current understanding of biochemical pathways controlling ceramide synthesis, production and action; influences of diet on ceramide levels; application of circulating ceramides as clinical biomarkers of metabolic disease; and molecular mechanisms linking ceramides to altered metabolism and survival of cells. Development of nutritional or pharmacological strategies to lower ceramides could have therapeutic value in a wide range of prevalent diseases.
饮食会影响多种慢性疾病的发病、进展和严重程度，包括心力衰竭、糖尿病、脂肪性肝炎和一部分癌症。在过去的二十年中，这些与肥胖相关的疾病的患病率和临床负担有所增加。这些代谢紊乱是由不适合储存脂肪的组织中异位脂质沉积引起的，导致脂肪毒性破坏细胞功能和存活。神经酰胺等鞘脂类是积累最多的有害和生物活性代谢物之一，因为它们参与选择性胰岛素抵抗、血脂异常、氧化应激和细胞凋亡。本文讨论了我们目前对控制神经酰胺合成、产生和作用的生化途径的理解；饮食对神经酰胺水平的影响；循环神经酰胺作为代谢性疾病临床生物标志物的应用；以及神经酰胺与细胞代谢和存活改变的分子机制。降低神经酰胺的营养或药物策略的发展可能在广泛的常见疾病中具有治疗价值。
