Hammerschmidt Philipp, Brüning Jens C
Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, Gleueler Strasse 50, 50931, Cologne, Germany.
Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Strasse 26, 50924, Cologne, Germany.
Cell Mol Life Sci. 2022 Jul 5;79(8):395. doi: 10.1007/s00018-022-04401-3.
Ceramides are a heterogeneous group of bioactive membrane sphingolipids that play specialized regulatory roles in cellular metabolism depending on their characteristic fatty acyl chain lengths and subcellular distribution. As obesity progresses, certain ceramide molecular species accumulate in metabolic tissues and cause cell-type-specific lipotoxic reactions that disrupt metabolic homeostasis and lead to the development of cardiometabolic diseases. Several mechanisms for ceramide action have been inferred from studies in vitro, but only recently have we begun to better understand the acyl chain length specificity of ceramide-mediated signaling in the context of physiology and disease in vivo. New discoveries show that specific ceramides affect various metabolic pathways and that global or tissue-specific reduction in selected ceramide pools in obese rodents is sufficient to improve metabolic health. Here, we review the tissue-specific regulation and functions of ceramides in obesity, thus highlighting the emerging concept of selectively inhibiting production or action of ceramides with specific acyl chain lengths as novel therapeutic strategies to ameliorate obesity-associated diseases.
神经酰胺是一类异质性的生物活性膜鞘脂，根据其特征性的脂肪酰链长度和亚细胞分布，在细胞代谢中发挥特定的调节作用。随着肥胖的进展，某些神经酰胺分子种类在代谢组织中积累，并引起细胞类型特异性的脂毒性反应，破坏代谢稳态，导致心脏代谢疾病的发生。从体外研究中已经推断出几种神经酰胺作用机制，但直到最近，我们才开始在体内生理学和疾病背景下更好地理解神经酰胺介导信号传导的酰链长度特异性。新的发现表明，特定的神经酰胺会影响各种代谢途径，并且肥胖啮齿动物中选定神经酰胺池的整体或组织特异性减少足以改善代谢健康。在此，我们综述了神经酰胺在肥胖中的组织特异性调节和功能，从而突出了选择性抑制具有特定酰链长度的神经酰胺产生或作用这一新兴概念，作为改善肥胖相关疾病的新型治疗策略。
