Lazaridis Ioannis I, Bosch Angela J T, Keller Lena, Low Andy J Y, Tamarelle Jeanne, Moser Seraina O, Winter Denise V, Gómez Cristina, Peterson Caspar J, Schneider Romano, Kraljević Marko, Odermatt Alex, Vonaesch Pascale, Peterli Ralph, Delko Tarik, Cavelti-Weder Claudia
Clarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Basel, Switzerland.
Clinic of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland.
Am J Physiol Endocrinol Metab. 2024 Jun 1;326(6):E819-E831. doi: 10.1152/ajpendo.00327.2023. Epub 2024 Apr 17.
One-anastomosis gastric bypass (OAGB) has gained importance as a simple, safe, and effective operation to treat morbid obesity. We previously found that Roux-en-Y gastric bypass surgery with a long compared with a short biliopancreatic limb (BPL) leads to improved weight loss and glucose tolerance in obese mice. However, it is not known whether a long BPL in OAGB surgery also results in beneficial metabolic outcomes. Five-week-old male C57BL/6J mice fed a high-fat diet (HFD) for 8 weeks underwent OAGB surgery with defined BPL lengths (5.5 cm distally of the duodenojejunal junction for short and 9.5 cm for long BPL), or sham surgery combined with caloric restriction. Weight loss, glucose tolerance, obesity-related comorbidities, endocrine effects, gut microbiota, and bile acids were assessed. Total weight loss was independent of the length of the BPL after OAGB surgery. However, a long BPL was associated with lower glucose-stimulated insulin on , and an improved glucose tolerance on after surgery. Moreover, a long BPL resulted in reduced total cholesterol, while there were no differences in the resolution of metabolic dysfunction-associated steatotic liver disease (MASLD) and adipose tissue inflammation. Tendencies of an attenuated hypothalamic-pituitary-adrenal (HPA) axis and aldosterone were present in the long BPL group. With both the short and long BPL, we found an increase in primary conjugated bile acids (pronounced in long BPL) along with a loss in bacterial and and simultaneous increase in , , and . In summary, OAGB surgery with a long compared with a short BPL led to similar weight loss, but improved glucose metabolism, lipid, and endocrine outcomes in obese mice, potentially mediated through changes in gut microbiota and related bile acids. Tailoring the BPL length in humans might help to optimize metabolic outcomes after bariatric surgery. Weight loss following OAGB surgery in obese mice was not influenced by BPL length, but a longer BPL was associated with improved metabolic outcomes, including glucose and lipid homeostasis. These changes could be mediated by bile acids upon altered gut microbiota. Further validation of these findings is required through a randomized human study.
单吻合口胃旁路术（OAGB）作为一种治疗病态肥胖的简单、安全且有效的手术，已变得越来越重要。我们之前发现，与短胆胰支（BPL）相比，长胆胰支的Roux-en-Y胃旁路手术能使肥胖小鼠体重减轻更多，葡萄糖耐量得到改善。然而，尚不清楚OAGB手术中长BPL是否也会带来有益的代谢结果。对8周龄高脂饮食（HFD）喂养8周的雄性C57BL/6J小鼠进行了具有特定BPL长度（十二指肠空肠交界处远端5.5厘米为短BPL，9.5厘米为长BPL）的OAGB手术，或假手术并结合热量限制。评估了体重减轻、葡萄糖耐量、肥胖相关合并症、内分泌效应、肠道微生物群和胆汁酸。OAGB手术后总体体重减轻与BPL长度无关。然而，长BPL与术后较低的葡萄糖刺激胰岛素水平以及改善的葡萄糖耐量相关。此外，长BPL可降低总胆固醇，而在代谢功能障碍相关脂肪性肝病（MASLD）和脂肪组织炎症的缓解方面没有差异。长BPL组存在下丘脑 - 垂体 - 肾上腺（HPA）轴和醛固酮减弱的趋势。无论BPL长短，我们都发现初级结合胆汁酸增加（长BPL中更明显），同时细菌 和 减少， 、 和 增加。总之，与短BPL相比，长BPL的OAGB手术导致类似的体重减轻，但改善了肥胖小鼠的葡萄糖代谢、脂质和内分泌结果，可能是通过肠道微生物群和相关胆汁酸的变化介导的。在人类中调整BPL长度可能有助于优化减肥手术后的代谢结果。肥胖小鼠OAGB手术后的体重减轻不受BPL长度影响，但较长的BPL与改善的代谢结果相关，包括葡萄糖和脂质稳态。这些变化可能由肠道微生物群改变后的胆汁酸介导。需要通过随机人体研究进一步验证这些发现。
