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

Onderzoeksgroep Kalsbeek
Publicatiejaar 2023
Gepubliceerd in Cell reports. Medicine
Auteur(s) 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

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.

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