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

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

  • Acta Physiol (Oxf). 2021 May;232(1):e13610. doi: 10.1111/apha.13610.
J Thomas Hannich 1,  Ursula Loizides-Mangold 2 3 4 5,  Flore Sinturel 2 3 4 5,  Takeshi Harayama 1,  Bart Vandereycken 6,  Camille Saini 7,  Pauline Gosselin 2 3 4 5 7,  Marie-Claude Brulhart-Meynet 2,  Maud Robert 8,  Stephanie Chanon 9,  Christine Durand 9,  Jonathan Paz Montoya 10,  Fabrice P A David 11,  Idris Guessous 7,  Zoltan Pataky 12,  Alain Golay 12,  François R Jornayvaz 2 4,  Jacques Philippe 2 4,  Emmanouil T Dermitzakis 4 5 13,  Steven A Brown 14,  Etienne Lefai 15,  Howard Riezman 1,  Charna Dibner 2 3 4 5
Affiliations

Affiliations

  • 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.
PMID: 33351229 DOI: 10.1111/apha.13610
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.

Keywords

1-deoxyceramide; Type 2 diabetes in lean and obese subjects; lipid metabolism; lipidomics; serum; visceral adipose tissue.

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