The obesity epidemic and its associated comorbidities present a looming challenge to health care delivery throughout the world. Obesity is characterized as a sterile inflammatory process within adipose tissues leading to dysregulated secretion of bioactive adipokines such as adiponectin and leptin, as well as systemic metabolic dysfunction. The majority of current obesity research has focused primarily on preclinical animal models in vivo and two-dimensional cell culture models in vitro. Neither of these generalized approaches is optimal due to interspecies variability, insufficient accuracy with respect to predicting human outcomes, and failure to recapitulate the three-dimensional (3D) microenvironment. Consequently, there is a growing demand and need for more sophisticated microphysiological systems to reproduce more physiologically accurate human white and brown/beige adipose depots. To address this research need, human and murine cell lines and primary cultures are being combined with bioscaffolds to create functional 3D environments that are suitable for metabolically active adipose organoids in both static and perfusion bioreactor cultures. The development of these technologies will have considerable impact on the future pace of discovery for novel small molecules and biologics designed to prevent and treat metabolic syndrome and obesity in humans. Furthermore, when these adipose tissue models are integrated with other organ systems they will have applicability to obesity-related disorders such as diabetes, nonalcoholic fatty liver disease, and osteoarthritis.

中文翻译：

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用于肥胖及其代谢合并症研究和发现的片上脂肪模型

肥胖流行及其相关合并症对全世界的医疗保健服务提出了迫在眉睫的挑战。肥胖的特征是脂肪组织内的无菌炎症过程，导致脂联素和瘦素等生物活性脂肪因子分泌失调，以及全身代谢功能障碍。目前大多数肥胖研究主要集中在体内的临床前动物模型和体外的二维细胞培养模型上. 由于种间变异性、预测人类结果的准确性不足以及无法概括三维 (3D) 微环境，这些通用方法都不是最佳方法。因此，对更复杂的微生理系统的需求和需求不断增长，以重现生理上更准确的人类白色和棕色/米色脂肪库。为了满足这一研究需求，人类和鼠类细胞系和原代培养物与生物支架相结合，以创建适用于静态和灌注生物反应器培养中代谢活跃的脂肪类器官的功能性 3D 环境。这些技术的发展将对旨在预防和治疗人类代谢综合征和肥胖症的新型小分子和生物制剂的未来发现速度产生重大影响。此外，当这些脂肪组织模型与其他器官系统整合时，它们将适用于与肥胖相关的疾病，如糖尿病、非酒精性脂肪肝和骨关节炎。