| Title |
SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes
|
|---|---|
| Published in |
Diabetologia, April 2017
|
| DOI | 10.1007/s00125-017-4261-z |
| Pubmed ID | |
| Authors |
Janna A. van Diepen, Joris H. Robben, Guido J. Hooiveld, Claudia Carmone, Mohammad Alsady, Lily Boutens, Melissa Bekkenkamp-Grovenstein, Anneke Hijmans, Udo F. H. Engelke, Ron A. Wevers, Mihai G. Netea, Cees J. Tack, Rinke Stienstra, Peter M. T. Deen |
| Abstract |
Obesity induces macrophages to drive inflammation in adipose tissue, a crucial step towards the development of type 2 diabetes. The tricarboxylic acid (TCA) cycle intermediate succinate is released from cells under metabolic stress and has recently emerged as a metabolic signal induced by proinflammatory stimuli. We therefore investigated whether succinate receptor 1 (SUCNR1) could play a role in the development of adipose tissue inflammation and type 2 diabetes. Succinate levels were determined in human plasma samples from individuals with type 2 diabetes and non-diabetic participants. Succinate release from adipose tissue explants was studied. Sucnr1 (-/-) and wild-type (WT) littermate mice were fed a high-fat diet (HFD) or low-fat diet (LFD) for 16 weeks. Serum metabolic variables, adipose tissue inflammation, macrophage migration and glucose tolerance were determined. We show that hypoxia and hyperglycaemia independently drive the release of succinate from mouse adipose tissue (17-fold and up to 18-fold, respectively) and that plasma levels of succinate were higher in participants with type 2 diabetes compared with non-diabetic individuals (+53%; p < 0.01). Sucnr1 (-/-) mice had significantly reduced numbers of macrophages (0.56 ± 0.07 vs 0.92 ± 0.15 F4/80 cells/adipocytes, p < 0.05) and crown-like structures (0.06 ± 0.02 vs 0.14 ± 0.02, CLS/adipocytes p < 0.01) in adipose tissue and significantly improved glucose tolerance (p < 0.001) compared with WT mice fed an HFD, despite similarly increased body weights. Consistently, macrophages from Sucnr1 (-/-) mice showed reduced chemotaxis towards medium collected from apoptotic and hypoxic adipocytes (-59%; p < 0.05). Our results reveal that activation of SUCNR1 in macrophages is important for both infiltration and inflammation of adipose tissue in obesity, and suggest that SUCNR1 is a promising therapeutic target in obesity-induced type 2 diabetes. The dataset generated and analysed during the current study is available in GEO with the accession number GSE64104, www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE64104 . |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 4 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 149 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 149 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 26 | 17% |
| Student > Ph. D. Student | 23 | 15% |
| Student > Bachelor | 22 | 15% |
| Researcher | 19 | 13% |
| Other | 5 | 3% |
| Other | 22 | 15% |
| Unknown | 32 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 40 | 27% |
| Agricultural and Biological Sciences | 18 | 12% |
| Medicine and Dentistry | 13 | 9% |
| Immunology and Microbiology | 11 | 7% |
| Neuroscience | 7 | 5% |
| Other | 23 | 15% |
| Unknown | 37 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 October 2023.
All research outputs
#6,967,697
of 25,483,400 outputs
Outputs from Diabetologia
#2,751
of 5,348 outputs
Outputs of similar age
#103,562
of 324,771 outputs
Outputs of similar age from Diabetologia
#57
of 71 outputs
Altmetric has tracked 25,483,400 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 5,348 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.7. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
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We're also able to compare this research output to 71 others from the same source and published within six weeks on either side of this one. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.