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Human CD206+ macrophages associate with diabetes and adipose tissue lymphoid clusters.
Muir, Lindsey A; Cho, Kae Won; Geletka, Lynn M; Baker, Nicki A; Flesher, Carmen G; Ehlers, Anne P; Kaciroti, Niko; Lindsly, Stephen; Ronquist, Scott; Rajapakse, Indika; O'Rourke, Robert W; Lumeng, Carey N.
Afiliación
  • Muir LA; Department of Pediatrics and.
  • Cho KW; Department of Pediatrics and.
  • Geletka LM; Department of Pediatrics and.
  • Baker NA; Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • Flesher CG; Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • Ehlers AP; Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • Kaciroti N; Department of Surgery, Ann Arbor Veterans Affairs Healthcare System, Ann Arbor, Michigan, USA.
  • Lindsly S; Center for Human Growth and Development, University of Michigan, Ann Arbor, Michigan, USA.
  • Ronquist S; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
  • Rajapakse I; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • O'Rourke RW; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • Lumeng CN; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
JCI Insight ; 7(3)2022 02 08.
Article en En | MEDLINE | ID: mdl-34990410
Increased adipose tissue macrophages (ATMs) correlate with metabolic dysfunction in humans and are causal in development of insulin resistance in mice. Recent bulk and single-cell transcriptomics studies reveal a wide spectrum of gene expression signatures possible for macrophages that depends on context, but the signatures of human ATM subtypes are not well defined in obesity and diabetes. We profiled 3 prominent ATM subtypes from human adipose tissue in obesity and determined their relationship to type 2 diabetes. Visceral adipose tissue (VAT) and s.c. adipose tissue (SAT) samples were collected from diabetic and nondiabetic obese participants to evaluate cellular content and gene expression. VAT CD206+CD11c- ATMs were increased in diabetic participants, were scavenger receptor-rich with low intracellular lipids, secreted proinflammatory cytokines, and diverged significantly from 2 CD11c+ ATM subtypes, which were lipid-laden, were lipid antigen presenting, and overlapped with monocyte signatures. Furthermore, diabetic VAT was enriched for CD206+CD11c- ATM and inflammatory signatures, scavenger receptors, and MHC II antigen presentation genes. VAT immunostaining found CD206+CD11c- ATMs concentrated in vascularized lymphoid clusters adjacent to CD206-CD11c+ ATMs, while CD206+CD11c+ were distributed between adipocytes. Our results show ATM subtype-specific profiles that uniquely contribute to the phenotypic variation in obesity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Glicoproteínas de Membrana / Receptores Inmunológicos / Tejido Adiposo / Regulación de la Expresión Génica / Diabetes Mellitus Tipo 2 / Macrófagos / Obesidad Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: JCI Insight Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Glicoproteínas de Membrana / Receptores Inmunológicos / Tejido Adiposo / Regulación de la Expresión Génica / Diabetes Mellitus Tipo 2 / Macrófagos / Obesidad Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: JCI Insight Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos