Nugent Julia L, Singh Amar, Wirth Keith M, Oppler Scott Hunter, Hocum Stone Laura, Janecek Jody L, Sheka Adam C, Kizy Scott, Moore Meghan E G, Staley Christopher, Hering Bernhard J, Ramachandran Sabarinathan, Ikramuddin Sayeed, Graham Melanie L
Department of Surgery, University of Minnesota, MN, USA.
Preclinical Research Center, Department of Surgery, University of Minnesota, 295 Animal Science/Veterinary Medicine Building, 1988 Fitch Avenue, St. Paul, MN 55108, USA.
iScience. 2021 Nov 10;24(12):103421. doi: 10.1016/j.isci.2021.103421. eCollection 2021 Dec 17.
The obesity epidemic significantly contributes to overall morbidity and mortality. Bariatric surgery is the gold standard treatment for obesity and metabolic dysfunction, yet the mechanisms by which it exerts metabolic benefit remain unclear. Here, we demonstrate a model of vertical sleeve gastrectomy (VSG) in nonhuman primates (NHP) that mimics the complexity and outcomes in humans. We also show that VSG confers weight loss and durable metabolic benefit, where equivalent caloric intake in shams resulted in significant weight gain following surgery. Furthermore, we show that VSG is associated with early, weight-independent increases in bile acids, short-chain fatty acids, and reduced visceral adipose tissue (VAT) inflammation with a polarization of VAT-resident immunocytes toward highly regulatory myeloid cells and Tregs. These data demonstrate that this strongly translational NHP model can be used to interrogate factors driving successful intervention to unravel the interplay between physiologic systems and improve therapies for obesity and metabolic syndrome.
肥胖流行对总体发病率和死亡率有显著影响。减重手术是肥胖和代谢功能障碍的金标准治疗方法，但其发挥代谢益处的机制仍不清楚。在此，我们展示了一种在非人灵长类动物（NHP）中进行的垂直袖状胃切除术（VSG）模型，该模型模拟了人类的复杂性和手术效果。我们还表明，VSG能带来体重减轻和持久的代谢益处，而假手术组在同等热量摄入的情况下，术后体重显著增加。此外，我们发现VSG与胆汁酸、短链脂肪酸的早期、与体重无关的增加以及内脏脂肪组织（VAT）炎症的减轻有关，VAT驻留免疫细胞向高度调节性髓样细胞和调节性T细胞极化。这些数据表明，这种具有强大转化能力的NHP模型可用于探究驱动成功干预的因素，以揭示生理系统之间的相互作用，并改善肥胖和代谢综合征的治疗方法。
