The short-term and long-term effects of bariatric/metabolic surgery on subcutaneous adipose tissue inflammation in humans.
The short-term and long-term effects of bariatric/metabolic surgery on subcutaneous adipose tissue inflammation in humans.
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DOI：
10.1016/j.metabol.2017.01.030
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Kratz M
中科院分区：
文献类型：
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作者：
Hagman DK;Larson I;Kuzma JN;Cromer G;Makar K;Rubinow KB;Foster-Schubert KE;van Yserloo B;Billing PS;Landerholm RW;Crouthamel M;Flum DR;Cummings DE;Kratz M
减肥/代谢手术后血糖稳态短期和长期改善的机制仍不完全清楚。为了研究脂肪组织炎症的减少是否在减肥/代谢手术后的代谢改善中发挥作用，无论是短期还是长期。肥胖者在减肥/代谢手术前(n=14)、术后1个月(n=9)、术后6~12个月(n=14)采集空腹血和腹部皮下脂肪组织，均未服用胰岛素或抗糖尿病药物。脂肪组织炎症通过整体组织基因表达和基于流式细胞术的组织白细胞定量相结合来评估。术后1个月体重减轻13.5±4.4kgp<；0.001)，糖耐量改善表现为3h口服葡萄糖耐量试验曲线下面积减少(−105±98 mmoL/L*分钟；p=0.009)和胰腺β细胞功能增强(胰岛素生成指数：+0.8±0.9pmoL/mmo1；p=0.032)，但胰岛素敏感性估计值无变化(松田胰岛素敏感指数[isi]；p=0.720)。此外，尽管全身炎症和脂肪组织中致炎基因表达的生物标志物保持不变，但脂肪组织中中性粒细胞的数量增加了15-20倍(p<；0.001)，而其他白细胞的数量增加较少。经过6-12个月的随访，体重较治疗前下降34.8±10.8 kg(p<；0.001)，糖耐量进一步改善(AUC葡萄糖−为2 76±2 2 9；p<；0.001)，胰岛素敏感性(松田：+4.6±3.2；p<；0.001)。此外，循环C-反应蛋白(−2.0±5.3 mg/dL；p=0.002)和血清脂联素(+1,358±1,406 pg/ml；p=0.003)的减少反映了全身炎症的改善。然而，与基线相比，脂肪组织中的白细胞浸润仍然增加，促炎症细胞因子的表达没有变化，而脂联素的表达有下降的趋势(p=0.069)。减肥/代谢手术后的短期和长期代谢改善都没有显著减少脂肪组织炎症的指标，这是通过测量炎症关键介质的基因表达以及通过流式细胞仪免疫表型分析和脂肪组织白细胞的定量来评估的。
The mechanisms mediating the short- and long-term improvements in glucose homeostasis following bariatric/metabolic surgery remain incompletely understood. 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. 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. 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). 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 cytometric immunophenotyping and quantification of adipose tissue leukocytes.