Type 2 diabetes is associated with increased circulating levels of 3-hydroxydecanoate activating GPR84 and neutrophil migration
Artikel i vetenskaplig tidskrift, 2022
Obesity and diabetes are associated with inflammation and altered plasma levels of several metabolites, which may be involved in disease progression. Some metabolites can activate G protein-coupled receptors (GPCRs) expressed on immune cells where they can modulate metabolic inflammation. Here, we find that 3-hydroxydecanoate is enriched in the circulation of obese individuals with type 2 diabetes (T2D) compared with nondiabetic controls. Administration of 3-hydroxydecanoate to mice promotes immune cell recruitment to adipose tissue, which was associated with adipose inflammation and increased fasting insulin levels. Furthermore, we demonstrate that 3-hydroxydecanoate stimulates migration of primary human and mouse neutrophils, but not monocytes, through GPR84 and Gαi signaling in vitro. Our findings indicate that 3-hydroxydecanoate is a T2D-associated metabolite that increases inflammatory responses and may contribute to the chronic inflammation observed in diabetes.
Cell biology
Pathophysiology
Immunology
Författare
Randi Bonke Mikkelsen
Köpenhamns universitet
Tulika Arora
Köpenhamns universitet
Kajetan Trošt
Köpenhamns universitet
Oksana Dmytriyeva
Köpenhamns universitet
Sune Kjærsgaard Jensen
Köpenhamns universitet
A. S. Meijnikman
Universiteit Van Amsterdam
L. E. Olofsson
Wallenberg Lab.
Dimitra Lappa
Chalmers, Biologi och bioteknik, Systembiologi
O. Aydin
Universiteit Van Amsterdam
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
V. E.A. Gerdes
Universiteit Van Amsterdam
Thomas Moritz
Köpenhamns universitet
A. W. Van de Laar
Spaarne Gasthuis
Maurits de Brauw
Spaarne Gasthuis
M. Nieuwdorp
Universiteit Van Amsterdam
S. Hjorth
Köpenhamns universitet
Thue W. Schwartz
Köpenhamns universitet
Fredrik Bäckhed
Sahlgrenska universitetssjukhuset
Köpenhamns universitet
Wallenberg Lab.
iScience
25890042 (eISSN)
Vol. 25 12 105683Ämneskategorier
Endokrinologi och diabetes
Immunologi
Immunologi inom det medicinska området
Styrkeområden
Hälsa och teknik
DOI
10.1016/j.isci.2022.105683
PubMed
36561890