Open AccessFeasibility of quantifying change in immune white cells in abdominal adipose tissue in response to an immune modulator in clinical obesity
Author(s) -
Fred R. Sattler,
Melissa Mert,
Ishwarya Sankaranarayanan,
Wendy J. Mack,
Lauriane Galle-Treger,
Evelyn González,
Lilit Baronikian,
Kyuwan Lee,
Pedram Shafiei Jahani,
Howard N. Hodis,
Christina M. DieliConwright,
Omid Akbari
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0237496
Subject(s) - medicine , peripheral blood mononuclear cell , adipose tissue , sitagliptin , inflammation , immune system , abdominal obesity , immunology , population , white adipose tissue , white blood cell , endocrinology , type 2 diabetes , diabetes mellitus , biology , metabolic syndrome , obesity , biochemistry , environmental health , in vitro
Background Obesity is often associated with inflammation in adipose tissue (AT) with release of mediators of atherogenesis. We postulated that it would be feasible to collect sufficient abdominal AT to quantify changes in a broad array of adaptive and innate mononuclear white cells in obese non-diabetic adults in response to a dipeptidyl protease inhibitor (DPP4i), known to inhibit activation of immune white cells. Methods Adults 18–55 years-of-age were screened for abdominal obesity and insulin resistance or impaired glucose tolerance but without known inflammatory conditions. Twenty-one eligible participants consented for study and were randomized 3:1 to receive sitagliptin (DPP4i) at 100mg or matching placebo daily for 28 days. Abdominal AT collected by percutaneous biopsy and peripheral blood mononuclear cell fractions were evaluated before and after treatment; plasma was stored for batch testing. Results Highly sensitive C-reactive protein, a global marker of inflammation, was not elevated in the study population. Innate lymphoid cells (ILC) type 3 (ILC-3) in abdominal AT decreased with active treatment compared with placebo (p = 0.04). Other immune white cells in AT and peripheral blood mononuclear cell (PBMC) fractions did not change with treatment compared to placebo (p>0.05); although ILC-2 declined in PBMCs (p = 0.007) in the sitagliptin treatment group. Two circulating biomarkers of atherogenesis, interferon-inducible protein-10 (IP-10) and sCD40L declined in plasma (p = 0.02 and p = 0.07, respectively) in the active treatment group, providing indirect validation of a net reduction in inflammation. Conclusions In this pilot study, two cell types of the innate lymphoid system, ILC-3 in AT and ILC-2 PBMCs declined during treatment and as did circulating biomarkers of atherogenesis. Changes in other immune cells were not demonstrable. The study showed that sufficient abdominal AT could be obtained to quantify white cells of both innate and adaptive immunity and to demonstrate changes during therapy with an immune inhibitor. Trial registration ClinicalTrials.gov identifier (NCT number): NCT02576