The Gut Microbiota Metabolite Succinate Promotes Adipose Tissue Browning in Crohn’s Disease

Autor: Monfort-Ferré, Diandra, Caro, Aleidis, Menacho, Margarita, Marti-Gallostra, Marc, Espina, Beatriz, Boronat-Toscano, Albert, Núñez Roa, Catalina, Seco, Jesús, Bautista, Michelle, Espín, Eloy, Megía, Ana, Vendrell, Joan, Fernández-Veledo, Sonia, Serena, Carolina, Universitat Autònoma de Barcelona
Přispěvatelé: Institut Català de la Salut, [Monfort-Ferré D, Boronat-Toscano A] Hospital Universitari de Tarragona Joan XXIII, Institut d’Investigació Sanitària Pere Virgili, Tarragona, Spain. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. [Caro A, Espina B] Colorectal Surgery Unit, Hospital Universitari Joan XXIII, Tarragona, Spain. [Menacho M] Digestive Unit, Hospital Universitari Joan XXIII, Tarragona, Spain. [Martí M, Espín E] Unitat de Cirurgia de Còlon i Recte, Servei de Cirurgia General, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2022
Předmět:
fenómenos microbiológicos::microbiota::microbiota intestinal [FENÓMENOS Y PROCESOS]
Microbiological Phenomena::Microbiota::Gastrointestinal Microbiome [PHENOMENA AND PROCESSES]
Adipose Tissue
White
Creeping fat
Succinic Acid
Gastroenterology
Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Inflammatory Bowel Diseases::Crohn Disease [DISEASES]
Bacteria translocation
General Medicine
Crohn
Malaltia de
Beige adipose tissue
enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::enfermedad inflamatoria intestinal::enfermedad de Crohn [ENFERMEDADES]
Gastrointestinal Microbiome
Succinic acid
Teixit adipós
Tissues::Connective Tissue::Adipose Tissue [ANATOMY]
SUCNR1
Crohn Disease
Adipose Tissue
Humans
Intestins - Microbiologia
tejidos::tejido conectivo::tejido adiposo [ANATOMÍA]
Uncoupling Protein 1
Zdroj: Scientia
ISSN: 1876-4479
1873-9946
DOI: 10.1093/ecco-jcc/jjac069
Popis: Succinic acid; Bacteria translocation; Beige adipose tissue Àcid succínic; Translocació de bacteris; Teixit adipós beige Ácido succínico; Translocación de bacterias; Tejido adiposo beige Background and Aims Crohn’s disease [CD] is associated with complex microbe–host interactions, involving changes in microbial communities, and gut barrier defects, leading to the translocation of microorganisms to surrounding adipose tissue [AT]. We evaluated the presence of beige AT depots in CD and questioned whether succinate and/or bacterial translocation promotes white-to-beige transition in adipocytes. Methods Visceral [VAT] and subcutaneous [SAT] AT biopsies, serum and plasma were obtained from patients with active [n = 21] or inactive [n = 12] CD, and from healthy controls [n = 15]. Adipose-derived stem cells [ASCs] and AT macrophages [ATMs] were isolated from VAT biopsies. Results Plasma succinate levels were significantly higher in patients with active CD than in controls and were intermediate in those with inactive disease. Plasma succinate correlated with the inflammatory marker high-sensitivity C-reactive protein. Expression of the succinate receptor SUCNR1 was higher in VAT, ASCs and ATMs from the active CD group than from the inactive or control groups. Succinate treatment of ASCs elevated the expression of several beige AT markers from controls and from patients with inactive disease, including uncoupling protein-1 [UCP1]. Notably, beige AT markers were prominent in ASCs from patients with active CD. Secretome profiling revealed that ASCs from patients with active disease secrete beige AT-related proteins, and co-culture assays showed that bacteria also trigger the white-to-beige switch of ASCs from patients with CD. Finally, AT depots from patients with CD exhibited a conversion from white to beige AT together with high UCP1 expression, which was corroborated by in situ thermal imaging analysis. Conclusions Succinate and bacteria trigger white-to-beige AT transition in CD. Understanding the role of beige AT in CD might aid in the development of therapeutic or diagnostic interventions. This study was supported by grants from the Spanish Ministry of Science and Innovation [PI18/00037 (Instituto de Salud Carlos III, ISCIII) to C.S.; PI17/01503 and PI20/00338 (ISCIII) to J.V. and RTI2018-093919 to S.F.-V.], co-financed by the European Regional Development Fund [ERDF] and a European Crohn’s and Colitis Organization grant to C.S. The Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders [CIBERDEM] [CB07708/0012] is an initiative of the Instituto de Salud Carlos ISCIII acknowledges support from the ‘Ramón y Cajal’ programme from the Ministerio de Educación y Ciencia [RYC2013-13186], co-financed by the ERDF. S.F.-V. acknowledge support from the ‘Miguel Servet’ tenure track programme [CP10/00438, CPII16/0008] from the Fondo de Investigación Sanitaria, co-financed by the ERDF. D.M.-F. acknowledges support from PERIS-PFI-Salut SLT01720000021.
Databáze: OpenAIRE
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