Type 2 diabetes is associated with increased circulating levels of 3-hydroxydecanoate activating GPR84 and neutrophil migration
Journal article, 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
Author
Randi Bonke Mikkelsen
University of Copenhagen
Tulika Arora
University of Copenhagen
Kajetan Trošt
University of Copenhagen
Oksana Dmytriyeva
University of Copenhagen
Sune Kjærsgaard Jensen
University of Copenhagen
A. S. Meijnikman
University of Amsterdam
L. E. Olofsson
Wallenberg Lab.
Dimitra Lappa
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
O. Aydin
University of Amsterdam
Jens B Nielsen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
V. E.A. Gerdes
University of Amsterdam
Thomas Moritz
University of Copenhagen
A. W. Van de Laar
Spaarne Hospital
Maurits de Brauw
Spaarne Hospital
M. Nieuwdorp
University of Amsterdam
S. Hjorth
University of Copenhagen
Thue W. Schwartz
University of Copenhagen
Fredrik Bäckhed
Sahlgrenska University Hospital
University of Copenhagen
Wallenberg Lab.
iScience
25890042 (eISSN)
Vol. 25 12 105683Subject Categories
Endocrinology and Diabetes
Immunology
Immunology in the medical area
Areas of Advance
Health Engineering
DOI
10.1016/j.isci.2022.105683
PubMed
36561890