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

Autor: Hannich JT; Department of Biochemistry, Faculty of Science, NCCR Chemical Biology, University of Geneva, Geneva, Switzerland., Loizides-Mangold U; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland.; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland., Sinturel F; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland.; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland., Harayama T; Department of Biochemistry, Faculty of Science, NCCR Chemical Biology, University of Geneva, Geneva, Switzerland., Vandereycken B; Department of Mathematics, University of Geneva, Geneva, Switzerland., Saini C; Department and Division of Primary Care Medicine, University Hospital of Geneva, Geneva, Switzerland., Gosselin P; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland.; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland.; Department and Division of Primary Care Medicine, University Hospital of Geneva, Geneva, Switzerland., Brulhart-Meynet MC; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland., Robert M; Department of Digestive and Bariatric Surgery, Edouard Herriot University Hospital, University, Lyon, France., Chanon S; CarMeN Laboratory, INSERM U1060, INRA 1397, University Lyon 1, Oullins, France., Durand C; CarMeN Laboratory, INSERM U1060, INRA 1397, University Lyon 1, Oullins, France., Paz Montoya J; Proteomics Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., David FPA; Gene Expression Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Guessous I; Department and Division of Primary Care Medicine, University Hospital of Geneva, Geneva, Switzerland., Pataky Z; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, Geneva, Switzerland., Golay A; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, Geneva, Switzerland., Jornayvaz FR; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland.; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Philippe J; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland.; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Dermitzakis ET; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland.; Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Brown SA; Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland., Lefai E; INRA, Unité de Nutrition Humaine, Université Clermont Auvergne, Paris, France., Riezman H; Department of Biochemistry, Faculty of Science, NCCR Chemical Biology, University of Geneva, Geneva, Switzerland., Dibner C; Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland.; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland.
Jazyk: angličtina
Zdroj: Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2021 May; Vol. 232 (1), pp. e13610. Date of Electronic Publication: 2021 Jan 14.
DOI: 10.1111/apha.13610
Abstrakt: 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.
(© 2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje