Type 2 diabetes is associated with increased circulating levels of 3-hydroxydecanoate activating GPR84 and neutrophil migration

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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.

OriginalsprogEngelsk
Artikelnummer105683
TidsskriftiScience
Vol/bind25
Udgave nummer12
Antal sider29
ISSN2589-0042
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
M.N. is in the SAB of Caelus Health and Kaleido Biosciences; however, none of these are relevant for the current manuscript. F.B. is founder and holds equity of Implexion Pharma AB and receives research funding from Biogaia AB, both of which are unrelated to this study.

Funding Information:
We thank Marianne Gregers Johansen and Nataliia Tiutcheva for technical assistance and Carina Onuczak Rosenberg for excellent mouse husbandry. We also thank Anna Hallén for making the graphical abstract. The BARIA study is funded by the Novo Nordisk Foundation ( NNF15OC0016798 ). Analyses was in part supported by the Transatlantic Networks of Excellence Award from the Leducq Foundation (17CVD01). M.N. is supported by a personal ZONMW-VICI grant 2020 [ 09150182010020 ] and F.B. is Torsten Söderberg Professor in Medicine and Wallenberg Scholar .

Publisher Copyright:
© 2022 The Author(s)

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