Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 94108, United States of America.
Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 94108, United States of America.
Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Jun;1867(6):159125. doi: 10.1016/j.bbalip.2022.159125. Epub 2022 Feb 23.
Obesity leads to persistent increases in immune responses that contribute to cardiometabolic pathologies such as diabetes and cardiovascular disease. Pro-inflammatory macrophages infiltrate the expanding fat mass, which leads to increased production of cytokines such as tumor necrosis factor-alpha. Moreover, saturated fatty acids enhance signaling through the toll-like receptors involved in innate immunity. Herein we discuss the evidence that ceramides-which are intermediates in the biosynthetic pathway that produces sphingolipids-are essential intermediates that link these inflammatory signals to impaired tissue function. We discuss the mechanisms linking these immune insults to ceramide production and review the numerous ceramide actions that alter cellular metabolism, induce oxidative stress, and stimulate apoptosis. Lastly, we evaluate the correlation of ceramides in humans with inflammation-linked cardiometabolic disease and discuss preclinical studies which suggest that ceramide-lowering interventions may be an effective strategy to treat or prevent such maladies.
肥胖会导致免疫反应持续增加，从而导致糖尿病和心血管疾病等代谢性疾病。促炎巨噬细胞浸润扩张的脂肪组织，导致细胞因子如肿瘤坏死因子-α的产生增加。此外，饱和脂肪酸增强了参与先天免疫的 toll 样受体的信号转导。本文讨论了证据表明，神经酰胺 - 是生物合成途径产生鞘脂的中间产物 - 是将这些炎症信号与组织功能障碍联系起来的必要中间产物。我们讨论了将这些免疫损伤与神经酰胺产生联系起来的机制，并回顾了许多改变细胞代谢、诱导氧化应激和刺激细胞凋亡的神经酰胺作用。最后，我们评估了人类神经酰胺与炎症相关的代谢性疾病的相关性，并讨论了临床前研究，这些研究表明，降低神经酰胺的干预可能是治疗或预防这些疾病的有效策略。
