Center for Research Acceleration by Digital Innovation (CRADI), Amgen Research, South San Francisco, CA 94080, USA.
Research China, Amgen Research, Shanghai 200020, China.
Cell Rep. 2023 Aug 29;42(8):112952. doi: 10.1016/j.celrep.2023.112952. Epub 2023 Aug 8.
Obesity and type 2 diabetes (T2D) remain major global healthcare challenges, and developing therapeutics necessitates using nonhuman primate models. Here, we present a transcriptomic and proteomic atlas of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of individuals with obesity, while extensive expression perturbations among T2D individuals are observed in many tissues such as the liver and kidney. Immune-response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Moreover, we highlight some potential therapeutic targets, including SLC2A1 and PCSK1 in obesity as well as SLC30A8 and SLC2A2 in T2D. Our study provides a resource for exploring the complex molecular mechanism of obesity and T2D and developing therapies for these diseases, with limitations including lack of hypothalamus, isolated islets of Langerhans, longitudinal data, and body fat percentage.
肥胖和 2 型糖尿病（T2D）仍然是全球主要的医疗保健挑战，开发治疗方法需要使用非人类灵长类动物模型。在这里，我们展示了一组食蟹猴所有主要器官的转录组和蛋白质组图谱，这些动物患有自发性肥胖或 T2D，并与健康对照组进行了比较。分子变化主要发生在肥胖个体的脂肪组织中，而 T2D 个体的许多组织（如肝脏和肾脏）中则观察到广泛的表达失调。肥胖和 T2D 中与免疫反应相关的途径被上调，而代谢和线粒体途径则被下调。此外，我们还强调了一些潜在的治疗靶点，包括肥胖症中的 SLC2A1 和 PCSK1 以及 T2D 中的 SLC30A8 和 SLC2A2。我们的研究为探索肥胖和 T2D 的复杂分子机制以及为这些疾病开发治疗方法提供了资源，但也存在一些局限性，包括缺乏下丘脑、胰岛的分离、纵向数据和体脂肪百分比。
