Low visceral adipose tissue regulatory T cells are associated with higher comorbidity severity in patients undergoing bariatric surgery

Surg Endosc. 2021 Jun;35(6):3131-3138. doi: 10.1007/s00464-020-07751-w. Epub 2020 Jun 22.

Abstract

Background: Adipose tissue (AT) inflammation is linked to the development of type 2 diabetes (T2DM) and atherosclerosis in murine models of obesity. Reduced AT regulatory T cells (Tregs), which are anti-inflammatory immune cells, play an important part in this pathogenesis, and we have shown that AT-Tregs are inversely correlated to increasing body-mass-index. The purpose of this study was to evaluate the association between AT-Treg abundance and comorbidity status in patients undergoing bariatric surgery (BS).

Methods: Visceral (intra-abdominal) AT was harvested at that time of primary BS (n = 80) and collagenase digested. AT-Treg abundance (CD4+/CD25+/FOXP3+) was characterized using flow cytometry from the AT stromal vascular fraction. The median AT-Treg abundance (3.03%) was utilized to define high (High-Tregs, n = 39) and low AT-Treg (low-Tregs, n = 38) abundance within this cohort. These two groups were compared in terms of baseline demographic data, preoperative obesity-related comorbidities, glycemic parameters, including insulin resistance (HOMA-IR).

Results: Age, excess body weight, and sex were not different between groups. Prevalence of hypertension, hyperlipidemia, or T2DM preoperatively were not different between groups. Compared to High-Tregs, patients with low-Tregs were more likely to have insulin-dependent type 2 diabetes (12.5% vs 2.9%, p = 0.04). Within patients with T2DM, low-Treg patients had higher plasma insulin levels compared to high-Tregs (31.8 (28.4-56.5) vs 15.5 (10.1-23.1), p = 0.04) and trended towards higher insulin resistance (HOMA-IR) (9.0 (5.3-18.3) vs 3.5 (2.2-7.7), p = 0.08). Within those diagnosed with hyperlipidemia, preoperative statin use was higher in Low-Treg patients compared to the control cohort (91% vs 50%, p = 0.056). Low-Treg patients with hypertension were more likely to need 2 + anti-hypertensive agents preoperatively compared to their counterparts (71% vs 44%, p = 0.058).

Conclusion: Within bariatric candidates, lower visceral AT-Treg abundance was associated with increased baseline medication requirements for type 2 diabetes, hypertension, and hyperlipidemia. This suggests that reduced AT-Tregs may be associated with higher obesity-related comorbidity severity.

Keywords: Adipose tissue inflammation; Bariatric surgery; Obesity; Regulatory T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bariatric Surgery*
  • Comorbidity
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / epidemiology
  • Humans
  • Intra-Abdominal Fat
  • Mice
  • T-Lymphocytes, Regulatory