脂质体
脂肪组织
2型糖尿病
鞘脂
脂类学
内分泌学
内科学
肥胖
糖尿病
生物
脂质代谢
医学
生物信息学
生物化学
作者
J. Thomas Hannich,Ursula Loizides‐Mangold,Flore Sinturel,Takeshi Harayama,Bart Vandereycken,Camille Saini,Pauline Gosselin,Marie‐Claude Brulhart‐Meynet,M. Robert,Stéphanie Chanon,Christine Durand,Jonathan Paz Montoya,Fabrice David,Idris Guessous,Zoltan Pataky,Alain Golay,François R. Jornayvaz,Jacques Philippe,Emmanouil T. Dermitzakis,Steven A. Brown,Étienne Lefai,Howard Riezman,Charna Dibner
摘要
Abstract Aim The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype. Methods To better understand the complex metabolic pattern of lean and obese T2D and non‐T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry‐based lipid analysis. Results Lipid homeostasis was strongly altered in a disease‐ and tissue‐specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso‐, diacyl‐ and ether‐phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1‐deoxyceramide accumulation in a disease‐specific manner in serum and visceral adipose tissue. The high amounts of non‐canonical 1‐deoxyceramide present in human adipose tissue most likely come from cell‐autonomous synthesis because 1‐deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments. Conclusion Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.
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