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| Pàgina inicial > Articles > Articles publicats > The Gut Microbiota Metabolite Succinate Promotes Adipose Tissue Browning in Crohn's Disease |
(Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitari Vall d'Hebron) (Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitari Vall d'Hebron) (Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitari Joan XXIII de Tarragona) (Hospital Universitari Joan XXIII de Tarragona)| Data: | 2022 |
| Resum: | 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. 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. 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. 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. |
| Ajuts: | Instituto de Salud Carlos III PI18/00037 Instituto de Salud Carlos III PI17/01503 Instituto de Salud Carlos III PI20/00338 Agencia Estatal de Investigación RTI2018-093919 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Succinic acid ; SUCNR1 ; Beige adipose tissue ; Bacteria translocation ; Creeping fat |
| Publicat a: | Journal of Crohn's and colitis, Vol. 16 (may 2022) , p. 1571-1583, ISSN 1876-4479 |
