Mitochondrial sourcing of interferogenic ligands and an autoantigen in human obesity-associated metaflammation.

Autor: Ghosh AR; Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Bandopadhyay P; Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India.; Academy of Scientific and Innovative Research, Ghaziabad, India., Sarkar J; Department of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Khanna S; Institute of Laparoscopic Surgery Hospitals, Kolkata, India., Chaudhuri T; Institute of Laparoscopic Surgery Hospitals, Kolkata, India., Tantia O; Institute of Laparoscopic Surgery Hospitals, Kolkata, India., Chakrabarti P; Academy of Scientific and Innovative Research, Ghaziabad, India.; Department of Cell Biology and Physiology, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Ganguly D; Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India.; Academy of Scientific and Innovative Research, Ghaziabad, India.
Jazyk: angličtina
Zdroj: Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2023 Sep; Vol. 31 (9), pp. 2229-2234. Date of Electronic Publication: 2023 Jul 26.
DOI: 10.1002/oby.23805
Abstrakt: Objective: Visceral adipose tissue (VAT) inflammation contributes to metabolic dysregulation in obesity. VAT recruitment and activation of plasmacytoid dendritic cells (pDCs) through toll-like receptor 9 (TLR9) recognition of self-DNA, leading to induction of type I interferons, are crucial innate triggers for this VAT inflammation. It was hypothesized that mitochondrial DNA (mtDNA) can contribute to TLR9 activation in VAT-recruited pDCs in obesity, and this study aimed to identify the carrier protein for ligand access to TLR9 and to explore whether this also provides for a source of autoantigens in this context.
Methods: VAT samples, used for gene expression studies as well as adipose explant cultures, were collected from patients with obesity (n = 54) and lean patients (n = 10). Supernatants from human pDC cultures, treated with adipose explant culture supernatants, were used for interferon α ELISA. Venous plasma, from patients with (n = 114) and without (n = 45) obesity, was used for an ELISA for autoantibodies.
Results: MtDNA from VAT in obesity, in complex with mitochondrial transcription factor A protein (TFAM), acts as interferogenic ligands for pDCs. Humoral autoreactivity against TFAM is also induced in obesity.
Conclusions: Interferogenic ligands and an autoantigen can be sourced from dysfunctional mitochondria in VAT of humans with obesity. Further therapeutic and prognostic potential for this immune mechanism in obesity warrants exploration.
(© 2023 The Obesity Society.)
Databáze: MEDLINE
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