The Short-term and Long-term Effects of Bariatric/Metabolic Surgery on Subcutaneous Adipose Tissue Inflammation in Humans

• Published in: Metabolism, clinical and experimental clinical and experimental, 2017-05, Vol.70, p.12-22
• Main Authors: Hagman, Derek K, Larson, Ilona, Kuzma, Jessica N, Cromer, Gail, Makar, Karen, Rubinow, Katya B, Foster-Schubert, Karen E, van Yserloo, Brian, Billing, Peter S, Landerholm, Robert W, Crouthamel, Matthew, Flum, David R, Cummings, David E, Kratz, Mario
• Format: Article
• Language: English
• Subjects: Adipose tissue inflammation; Bariatric surgery; Bariatric Surgery - methods; Endocrinology & Metabolism; Female; Gene Expression Profiling; Humans; Immunophenotyping; Inflammation - surgery; Insulin Resistance; Leukocyte Count; Male; Metabolic surgery; Metabolism; Subcutaneous Fat - pathology; Subcutaneous Fat - surgery; Time Factors; Weight Loss
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2017.01.030

Abstract Context The mechanisms mediating the short- and long-term improvements in glucose homeostasis following bariatric/metabolic surgery remain incompletely understood. Objective To investigate whether a reduction in adipose tissue inflammation plays a role in the metabolic improvements seen after bariatric/metabolic surgery, both in the short-term and longer-term. Design Fasting blood and subcutaneous abdominal adipose tissue were obtained before (n = 14), at one month (n = 9), and 6-12 months (n = 14) after bariatric/metabolic surgery from individuals with obesity who were not on insulin or anti-diabetes medication. Adipose tissue inflammation was assessed by a combination of whole-tissue gene expression and flow cytometry-based quantification of tissue leukocytes. Results One month after surgery, body weight was reduced by 13.5 ± 4.4 kg (p < 0.001), with improvements in glucose tolerance reflected by a decrease in area-under-the-curve (AUC) glucose in 3-h oral glucose tolerance tests (-105 ± 98 mmol/L*min; p = 0.009) and enhanced pancreatic β-cell function (insulinogenic index: + 0.8 ± 0.9 pmol/mmol; p = 0.032), but no change in estimated insulin sensitivity (Matsuda insulin sensitivity index [ISI]; p = 0.720). Furthermore, although biomarkers of systemic inflammation and pro-inflammatory gene expression in adipose tissue remained unchanged, the number of neutrophils increased in adipose tissue 15-20 fold (p < 0.001), with less substantial increases in other leukocyte populations. By the 6-12 month follow-up visit, body weight was reduced by 34.8 ± 10.8 kg (p < 0.001) relative to baseline, and glucose tolerance was further improved (AUC glucose -276 ± 229; p < 0.001) along with estimated insulin sensitivity (Matsuda ISI: + 4.6 ± 3.2; p < 0.001). In addition, improvements in systemic inflammation were reflected by reductions in circulating C-reactive protein (CRP; -2.0 ± 5.3 mg/dL; p = 0.002), and increased serum adiponectin (+ 1,358 ± 1,406 pg/mL; p = 0.003). However, leukocyte infiltration of adipose tissue remained elevated relative to baseline, with pro-inflammatory cytokine mRNA expression unchanged, while adiponectin mRNA expression trended downward (p = 0.069). Conclusion Both the short- and longer-term metabolic improvements following bariatric/metabolic surgery occur without significant reductions in measures of adipose tissue inflammation, as assessed by measuring the expression of genes encoding key mediators of inflammation and by flow cy