SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:28382382", "kind": "science-record", "revision": 8, "content_hash": "sha256:4d5e57b9d79dc36ea3528a4cae0aef3aa1235fea44677478fe6667bdb2e3a012", "created_at": "2026-11-01T15:40:25Z", "updated_at": "2026-11-01T22:42:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes.", "doi": "10.1007/s00125-017-4261-z", "pmid": "28382382", "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"], "journal": "Diabetologia", "year": 2017, "abstract": "AIMS/HYPOTHESIS: 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.\nMETHODS: 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.\nRESULTS: 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).\nCONCLUSIONS/INTERPRETATION: 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.\nDATA AVAILABILITY: 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 .", "claims": [{"id": "claim-method", "statement": "Statistical comparisons between two groups were calculated using a Student’s t test. Differences between four groups were tested with ANOVA, followed by post hoc Bonferroni correction.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28382382", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "Statistical comparisons between two groups were calculated using a Student’s t test. Differences between four groups were tested with ANOVA, followed by post hoc Bonferroni correction."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GEO dataset generated and analysed during the current study are available under data set accession number GSE64104, www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE64104. 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All other datasets generated during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study found that activation of SUCNR1 in macrophages is important for infiltration and inflammation of adipose tissue in obesity and may be a therapeutic target for obesity-induced type 2 diabetes; two-group comparisons used Student’s t test, four-group comparisons used ANOVA with post hoc Bonferroni correction, and the source microarray dataset is available through GEO under accession GSE64104.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28382382", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "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."}, {"asset": "source:pmid:28382382", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study found that activation of SUCNR1 in macrophages is important for infiltration and inflammation of adipose tissue in obesity and may be a therapeutic target for obesity-induced type 2 diabetes; two-group comparisons used Student’s t test, four-group comparisons used ANOVA with post hoc Bonferroni correction, and the source microarray dataset is available through GEO under accession GSE64104.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:28382382"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Sucnr1 -/- and wild-type (WT) littermate mice were fed a high-fat diet (HFD) or low-fat diet (L", "endently drive the release of succinate from mouse adipose tissue (17-fold and up to 18-fold, r", "nr1 −/− wild-type (WT) littermate offspring. Mice were housed under standardised conditions (12 h d", "/12 h light cycle). Unless stated otherwise, mice were fed ad libitum. Animal experiments were appr"], "order_basis": "paper_text_order:772", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["for further analysis. 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