Translational & Integrative Gastrointestinal & Endocrine Research (TIGER) Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Rd, Baton Rouge, LA, USA.
Integrated Physiology & Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Surg Endosc. 2023 Nov;37(11):8810-8817. doi: 10.1007/s00464-023-10351-z. Epub 2023 Aug 24.
The obesity pandemic has worsened global disease burden, including type 2 diabetes, cardiovascular disease, and cancer. Metabolic/bariatric surgery (MBS) is the most effective and durable obesity treatment, but the mechanisms underlying its long-term weight loss efficacy remain unclear. MBS drives substrate oxidation that has been linked to improvements in metabolic function and improved glycemic control that are potentially mediated by mitochondria-a primary site of energy production. As such, augmentation of intestinal mitochondrial function may drive processes underlying the systemic metabolic benefits of MBS. Herein, we applied a highly sensitive technique to evaluate intestinal mitochondrial function ex vivo in a mouse model of MBS.
Mice were randomized to surgery, sham, or non-operative control. A simplified model of MBS, ileal interposition, was performed by interposition of a 2-cm segment of terminal ileum into the proximal bowel 5 mm from the ligament of Treitz. After a four-week recovery period, intestinal mucosa of duodenum, jejunum, ileum, and interposed ileum were assayed for determination of mitochondrial respiratory function. Citrate synthase activity was measured as a marker of mitochondrial content.
Ileal interposition was well tolerated and associated with modest body weight loss and transient hypophagia relative to controls. Mitochondrial capacity declined in the native duodenum and jejunum of animals following ileal interposition relative to controls, although respiration remained unchanged in these segments. Similarly, ileal interposition lowered citrate synthase activity in the duodenum and jejunum following relative to controls but ileal function remained constant across all groups.
Ileal interposition decreases mitochondrial volume in the proximal intestinal mucosa of mice. This change in concentration with preserved respiration suggests a global mucosal response to segment specific nutrition signals in the distal bowel. Future studies are required to understand the causes underlying these mitochondrial changes.
肥胖症大流行使全球疾病负担恶化，包括 2 型糖尿病、心血管疾病和癌症。代谢/减重手术（MBS）是最有效和持久的肥胖症治疗方法，但它长期减肥效果的机制仍不清楚。MBS 驱动底物氧化，与代谢功能的改善和血糖控制的改善有关，这些改善可能由线粒体介导，线粒体是能量产生的主要部位。因此，增强肠道线粒体功能可能会促进 MBS 对全身代谢益处的相关过程。在此，我们应用一种高灵敏度技术，在 MBS 的小鼠模型中评估肠道线粒体功能的离体情况。
将小鼠随机分为手术组、假手术组或非手术对照组。通过将 2cm 末端回肠段插入Treitz 韧带近端肠段 5mm 处，进行简化的 MBS 模型，即回肠间置术。经过四周的恢复期，测定十二指肠、空肠、回肠和间置回肠的肠黏膜，以确定线粒体呼吸功能。柠檬酸合酶活性作为线粒体含量的标志物进行测量。
回肠间置术耐受性良好，与对照组相比，动物体重减轻适度且短暂出现食欲减退。与对照组相比，回肠间置术后，动物的固有十二指肠和空肠中的线粒体容量下降，但这些部位的呼吸仍保持不变。同样，回肠间置术后，十二指肠和空肠中的柠檬酸合酶活性相对于对照组降低，但各组间的回肠功能保持不变。
回肠间置术降低了小鼠近端肠黏膜的线粒体体积。这种浓度的变化与呼吸保持不变表明，远端肠段的特定营养信号会引起整个黏膜的反应。需要进一步的研究来了解这些线粒体变化的原因。
