Ether lipids, sphingolipids, and toxic 1‐deoxyceramides as hallmarks for lean and obese type 2 diabetic patients

摘要: Aim The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by further promote the development of T2D, accumulation toxic lipid metabolites serum peripheral organs may contribute to diabetic phenotype. Methods To better understand complex metabolic pattern lean obese T2D non-T2D individuals, we analysed profile human serum, skeletal muscle visceral adipose tissue two cohorts systematic mass spectrometry-based analysis. Results Lipid homeostasis was strongly disease- tissue-specific manner, allowing us define signatures associated with from those that were independent. changes encompassed lyso-, diacyl- ether-phospholipids. Moreover, strong sphingolipids included cytotoxic 1-deoxyceramide disease-specific manner tissue. high amounts non-canonical present most likely come cell-autonomous synthesis because production increased upon differentiation adipocytes mouse cell culture experiments. Conclusion Taken together, observed lipidome will facilitate identification patient subgroups represent an important step towards personalized medicine diabetes.