J Thomas Hannich1, Ursula Loizides-Mangold2,3,4,5, Flore Sinturel2,3,4,5, Takeshi Harayama1, Bart Vandereycken6, Camille Saini7, Pauline Gosselin2,3,4,5,7, Marie-Claude Brulhart-Meynet2, Maud Robert8, Stephanie Chanon9, Christine Durand9, Jonathan Paz Montoya10, Fabrice P A David11, Idris Guessous7, Zoltan Pataky12, Alain Golay12, François R Jornayvaz2,4, Jacques Philippe2,4, Emmanouil T Dermitzakis4,5,13, Steven A Brown14, Etienne Lefai15, Howard Riezman1, Charna Dibner2,3,4,5. 1. Department of Biochemistry, Faculty of Science, NCCR Chemical Biology, University of Geneva, Geneva, Switzerland. 2. Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland. 3. Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 4. Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 5. Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. 6. Department of Mathematics, University of Geneva, Geneva, Switzerland. 7. Department and Division of Primary Care Medicine, University Hospital of Geneva, Geneva, Switzerland. 8. Department of Digestive and Bariatric Surgery, Edouard Herriot University Hospital, University, Lyon, France. 9. CarMeN Laboratory, INSERM U1060, INRA 1397, University Lyon 1, Oullins, France. 10. Proteomics Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. 11. Gene Expression Core Facility, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. 12. Division of Endocrinology, Diabetes, Nutrition and Patient Education, Department of Medicine, WHO Collaborating Centre, University Hospital of Geneva, University of Geneva, Geneva, Switzerland. 13. Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 14. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland. 15. INRA, Unité de Nutrition Humaine, Université Clermont Auvergne, Paris, France.
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.
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.
Authors: Emily Olson; Jung H Suh; Jean-Marc Schwarz; Susan M Noworolski; Grace M Jones; John R Barber; Ayca Erkin-Cakmak; Kathleen Mulligan; Robert H Lustig; Michele Mietus-Snyder Journal: Nutrients Date: 2022-03-30 Impact factor: 6.706