| Summary: | 博士 === 國立臺灣大學 === 臨床醫學研究所 === 104 === Obesity and type 2 diabetes (T2DM) are both characterized as a state of chronic low-grade inflammation. There are several possible biomarkers for obesity and T2DM, but the relationships and detailed mechanisms were not well discovered. Bariatric surgery not only reduces body weight, but also improves and prevents obesity related disorders, including T2DM. Different procedures lead to different pathophysiological changes. Therefore, bariatric surgery provides a good tool to study the detail mechanisms of obesity, T2DM, and the associated biomarkers.
Fetuin-A and matrix metalloproteinase-7 (MMP-7) are both T2DM-associated markers. The first part of my study aimed to investigate the changes of fetuin-A and MMP-7 in obese subjects with and without T2DM after bariatric surgery. We enrolled 130 obese subjects that received bariatric surgery, including 41 Roux-en-Y gastric bypass (RYGB), 67 mini-gastric bypass (MGB), and 22 sleeve gastrectomy (SG) patients. Forty-three patients suffered from T2DM prior to surgery, and only five remained diabetic one year after surgery. The fetuin-A and MMP-7 levels are both higher in obese T2DM than non-T2DM subjects. The level of fetuin-A is reduced one year after RYGB, MGB, and SG, but the level of MMP-7 remains unchanged. In multi-variate analyses, the preoperative fetuin-A was significantly related to the diastolic blood pressure (DBP) and glycosylated hemoglobin (HbA1c), while the postoperative fetuin-A was independently related to the waist-to-hip ratio and HbA1c. Moreover, the preoperative MMP-7 level was significantly related to age, DBP, aspartate transaminase, alanine transaminase, and gamma-glutamyl transferase (rGT), while the postoperative MMP-7 level was independently related to age and rGT.
Recent studies have shown serum lipopolysaccharide binding protein (LBP) is associated with obesity and related metabolic disorder. In the second part, we investigated LBP concentration and its associations with clinical variables after bariatric surgery. One hundred and seventy eight obese subjects receiving different bariatric surgeries and 38 normal weight individuals were enrolled. Serum LBP levels were higher in the obese participants than in the normal weight participants at baseline, and significantly decreased one year after bariatric surgery in the obese group. In the bariatric participants, after multivariate analyses, preoperative LBP and the change of LBP with surgery were independently associated only with hs-CRP and the change of hs-CRP respectively, while none of the postoperative variables was independently associated with LBP. The relationship between LBP and hs-CRP disappeared after bariatric surgery.
Gastrointestinal bypass changes the gut microbiota and decreases systemic endotoxemia in obese subjects. Epithelial barrier integrity is crucial for confining enteric bacteria in the lumen and preventing gut-derived endotoxemia. Therefore, the third part of our study aimed to evaluate the changes in intestinal permeability and gut barrier between rats receiving Roux-en-Y duodenojejunal bypass (DJB) or sham operation (SO). Enteric bacterial numbers were increased in the alimentary and common limbs after DJB. Reduced dextran permeability was found in the alimentary limb, common limb, and colon after DJB. Moreover, increased villus height and crypt depth were found to be associated with higher mucosal levels of occludin and proliferating cell nuclear antigen levels in the alimentary and common limbs after DJB. In summary, DJB in rats altered gut microbiota, and reduced intestinal permeability due to increased epithelial proliferation and tight junctional protein expression. Our results show that bypass surgery led to fortification of the intestinal barrier functions, which may provide an explanation for the decreased risk of systemic endotoxemia in postoperative patients.
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