Circadian organization of lipid landscape is perturbed in type 2 diabetic patients

Flore Sinturel; Simona Chera; Marie-Claude Brulhart-Meynet; Jonathan Paz Montoya; Dirk Jan Stenvers; Peter H Bisschop; Andries Kalsbeek; Idris Guessous; François R Jornayvaz; Jacques Philippe; Steven A Brown; Giovanni D'Angelo; Howard Riezman; Charna Dibner

doi:10.1016/j.xcrm.2023.101299

Circadian organization of lipid landscape is perturbed in type 2 diabetic patients

Cell Rep Med. 2023 Dec 19;4(12):101299. doi: 10.1016/j.xcrm.2023.101299. Epub 2023 Nov 27.

Authors

Affiliations

¹ Division of Thoracic and Endocrine Surgery, Department of Surgery, University Hospitals of Geneva, 1211 Geneva, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva, Switzerland.
² Division of Thoracic and Endocrine Surgery, Department of Surgery, University Hospitals of Geneva, 1211 Geneva, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva, Switzerland; Department of Clinical Science, University of Bergen, 5021 Bergen, Norway.
³ Division of Thoracic and Endocrine Surgery, Department of Surgery, University Hospitals of Geneva, 1211 Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
⁴ Institute of Bioengineering, School of Life Sciences, EPFL, 1015 Lausanne, Switzerland.
⁵ Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, 1105 AZ, the Netherlands; Amsterdam Gastroenterology, Endocrinology and Metabolism (AGEM), Amsterdam University Medical Centers, Amsterdam, 1105 AZ, the Netherlands.
⁶ Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, 1105 AZ, the Netherlands; Amsterdam Gastroenterology, Endocrinology and Metabolism (AGEM), Amsterdam University Medical Centers, Amsterdam, 1105 AZ, the Netherlands; Laboratory for Endocrinology, Department of Clinical Chemistry, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, 1105 AZ, the Netherlands; Netherlands Institute for Neuroscience (NIN), Royal Dutch Academy of Arts and Sciences (KNAW), Amsterdam, 1105 BA, the Netherlands.
⁷ Department and Division of Primary Care Medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland.
⁸ Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Division of Endocrinology, Diabetes, Nutrition, and Therapeutic Patient Education, Department of Medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland.
⁹ Division of Endocrinology, Diabetes, Nutrition, and Therapeutic Patient Education, Department of Medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland.
¹⁰ Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland.
¹¹ Department of Biochemistry, Faculty of Science, NCCR Chemical Biology, University of Geneva, 1211 Geneva, Switzerland.
¹² Division of Thoracic and Endocrine Surgery, Department of Surgery, University Hospitals of Geneva, 1211 Geneva, Switzerland; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), 1211 Geneva, Switzerland. Electronic address: charna.dibner@unige.ch.

Abstract

Lipid homeostasis in humans follows a diurnal pattern in muscle and pancreatic islets, altered upon metabolic dysregulation. We employ tandem and liquid-chromatography mass spectrometry to investigate daily regulation of lipid metabolism in subcutaneous white adipose tissue (SAT) and serum of type 2 diabetic (T2D) and non-diabetic (ND) human volunteers (n = 12). Around 8% of ≈440 lipid metabolites exhibit diurnal rhythmicity in serum and SAT from ND and T2D subjects. The spectrum of rhythmic lipids differs between ND and T2D individuals, with the most substantial changes observed early morning, as confirmed by lipidomics in an independent cohort of ND and T2D subjects (n = 32) conducted at a single morning time point. Strikingly, metabolites identified as daily rhythmic in both serum and SAT from T2D subjects exhibit phase differences. Our study reveals massive temporal and tissue-specific alterations of human lipid homeostasis in T2D, providing essential clues for the development of lipid biomarkers in a temporal manner.

Keywords: 1-deoxyceramides; DAGs; TAGs; glycerophosphopholipids; human circadian system; lipidomics; serum; sphingolipids; subcutaneous white adipose tissue; type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue, White / metabolism
Diabetes Mellitus, Type 2* / metabolism
Humans
Lipid Metabolism* / physiology
Lipids
Subcutaneous Fat / metabolism

Substances

Lipids