Abstract

Objective: Myeloid cells dominate metabolic disease-associated inflammation (metaflammation) in mouse obesity, but the contributions of myeloid cells to the peripheral inflammation that fuels sequelae of human obesity are untested. This study used unbiased approaches to rank contributions of myeloid and T cells to peripheral inflammation in people with obesity across the spectrum of metabolic health. Methods: Peripheral blood mononuclear cells (PBMCs) from people with obesity with or without prediabetes or type 2 diabetes were stimulated with T cell-targeting CD3/CD28 or myeloid-targeting lipopolysaccharide for 20 to 72 hours to assess cytokine production using Bio-Plex. Bioinformatic modeling ranked cytokines with respect to their predictive power for metabolic health. Intracellular tumor necrosis factor α was quantitated as a classical indicator of metaflammation. Results: Cytokines increased over 72 hours following T cell-, but not myeloid-, targeted stimulation to indicate that acute myeloid inflammation may shift to T cell inflammation over time. T cells contributed more tumor necrosis factor α to peripheral inflammation regardless of metabolic status. Bioinformatic combination of cytokines from all cohorts, stimuli, and time points indicated that T cell-targeted stimulation was most important for differentiating inflammation in diabetes, consistent with previous identification of a mixed T helper type 1/T helper type 17 cytokine profile in diabetes. Conclusions: T cells dominate peripheral inflammation in obesity; therefore, targeting T cells may be an effective approach for prevention/management of metaflammation.

Original languageEnglish
Pages (from-to)1983-1994
Number of pages12
JournalObesity
Volume30
Issue number10
DOIs
StatePublished - Oct 2022

Bibliographical note

Funding Information:
This work was supported by NIH Training Grants T32 DK007778 and TL1 UL1TR001998 (Gabriella H. Pugh), R01DK108056 (Barbara S. Nikolajczyk and Philip A. Kern), the Shared Resource Facility of the University of Kentucky Markey Cancer Center P30 CA177558, University of Kentucky College of Medicine (Barbara S. Nikolajczyk), Barnstable Brown Diabetes and Obesity Center (Barbara S. Nikolajczyk and Philip A. Kern), the Center for Clinical and Translational Research (UL1TR000117), and the NIH National Center for Advancing Translational Sciences UL1TR001998 (Philip A. Kern).

Funding Information:
The authors thank Dr. Elizabeth Proctor (Pennsylvania State University) and Dr. Doug Lauffenberger (Massachusetts Institute of Technology) for providing valuable insights on data troubleshooting and bioinformatic analysis, respectively. Dr. Jamie Sturgill brainstormed explanations for Kentucky versus Boston metro differences.

Publisher Copyright:
© 2022 The Obesity Society.

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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