Seyfried Florian, Springer Rebecca, Hoffmann Annett, Gruber Maximilian, Otto Christoph, Schlegel Nicolas, Hankir Mohammed K
Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, 97080, Germany.
Metabol Open. 2022 Oct 2;17:100212. doi: 10.1016/j.metop.2022.100212. eCollection 2023 Mar.
Roux-en-Y gastric bypass surgery (RYGB) improves glycemic control in individuals with severe obesity beyond the effects of weight loss alone. To identify potential underlying mechanisms, we asked how equivalent weight loss from RYGB and from chronic caloric restriction impact gut release of the metabolically beneficial cytokine interleukin-22 (Il-22).
Obese male Zucker fatty rats were randomized into sham-operated (Sham), RYGB, and sham-operated, body weight-matched to RYGB (BWM) groups. Food intake and body weight were measured regularly for 4 weeks. An oral glucose tolerance test (OGTT) was performed on postoperative day 27. Portal vein plasma, systemic plasma, and whole-wall samples from throughout the gut were collected on postoperative day 28. Gut 22 mRNA expression was determined by real-time quantitative PCR. Plasma Il-22 levels were determined by enzyme-linked immunosorbant assay (ELISA).
RYGB and BWM rats had lower food intake and body weight as well as superior blood glucose clearing capability compared with Sham rats. RYGB rats also had superior blood glucose clearing capability compared with BWM rats despite having similar body weights and higher food intake. 22 mRNA expression was approximately 100-fold higher specifically in the upper jejunum in RYGB rats compared with Sham rats. Il-22 protein was only detectable in portal vein (34.1 ± 9.4 pg/mL) and systemic (46.9 ± 10.5 pg/mL) plasma in RYGB rats. Area under the curve of blood glucose during the OGTT, but not food intake or body weight, negatively correlated with portal vein and systemic plasma Il-22 levels in RYGB rats.
These results suggest that induction of gut Il-22 release might partly account for the weight loss-independent improvements in glycemic control after RYGB, and further support the use of this cytokine for the treatment of metabolic disease.
Roux-en-Y胃旁路手术（RYGB）可改善重度肥胖个体的血糖控制，其效果不仅仅是体重减轻。为了确定潜在的潜在机制，我们研究了RYGB导致的同等体重减轻与慢性热量限制对代谢有益细胞因子白细胞介素-22（Il-22）肠道释放的影响。
将肥胖雄性Zucker脂肪大鼠随机分为假手术组（Sham）、RYGB组以及体重与RYGB组匹配的假手术组（BWM）。定期测量4周内的食物摄入量和体重。在术后第27天进行口服葡萄糖耐量试验（OGTT）。在术后第28天收集门静脉血浆、全身血浆以及整个肠道的全壁样本。通过实时定量PCR测定肠道Il-22 mRNA表达。采用酶联免疫吸附测定（ELISA）法测定血浆Il-22水平。
与Sham大鼠相比，RYGB组和BWM组大鼠的食物摄入量和体重较低，血糖清除能力更强。尽管RYGB组大鼠体重相似且食物摄入量更高，但其血糖清除能力仍优于BWM组大鼠。与Sham大鼠相比，RYGB组大鼠空肠上段的Il-22 mRNA表达约高100倍。仅在RYGB组大鼠的门静脉（34.1±9.4 pg/mL）和全身血浆（46.9±10.5 pg/mL）中检测到Il-22蛋白。在RYGB组大鼠中，OGTT期间血糖曲线下面积与门静脉和全身血浆Il-22水平呈负相关，而食物摄入量或体重与Il-22水平无此相关性。
这些结果表明，肠道Il-22释放的诱导可能部分解释了RYGB术后血糖控制方面与体重减轻无关的改善，并进一步支持将这种细胞因子用于治疗代谢性疾病。
