Baker Nicki A, Muir Lindsey A, Washabaugh Alexandra R, Neeley Christopher K, Chen Sophie Yu-Pu, Flesher Carmen G, Vorwald John, Finks Jonathan F, Ghaferi Amir A, Mulholland Michael W, Varban Oliver A, Lumeng Carey N, O'Rourke Robert W
Department of Surgery.
Department of Pediatrics and Communicable Diseases.
J Clin Endocrinol Metab. 2017 Mar 1;102(3):1032-1043. doi: 10.1210/jc.2016-2915.
The role of the extracellular matrix (ECM) in regulating adipocyte metabolism in the context of metabolic disease is poorly defined.
The objective of this study was to define the metabolic phenotype of adipocytes associated with human diabetes (DM) and the role of the ECM in regulating adipocyte metabolism.
Adipose tissues from obese patients were studied in standard 2-dimensional (2D) cell culture and an in vitro model of decellularized adipose tissue ECM repopulated with human adipocytes, and results were correlated with DM status.
This study was conducted at the Academic University Medical Center and Veteran's Administration Hospital.
Seventy patients with morbid obesity undergoing bariatric surgery were included in the study.
Visceral and subcutaneous adipose tissues were collected at the time of bariatric surgery.
This study used metabolic assays for glucose uptake, lipolysis, and lipogenesis in adipocytes in 2D cell culture and 3-dimensional ECM culture.
Adipocytes from subjects with DM manifest decreased glucose uptake and decreased lipolysis in 2D culture. ECM supports differentiation of mature adipocytes and recapitulates DM-specific differences in adipocyte metabolism observed in 2D culture. ECM from subjects without DM partially rescues glucose uptake and lipolytic defects in adipocytes from subjects with DM, whereas ECM from subjects with DM impairs glucose uptake in adipocytes from subjects without DM.
DM is associated with adipocyte metabolic dysfunction. The ECM regulates adipocyte metabolism. Nondiabetic ECM rescues metabolic dysfunction in DM adipocytes, whereas DM ECM imparts features of metabolic dysfunction to nondiabetic adipocytes. These findings suggest the ECM as a target for manipulating adipose tissue metabolism.
细胞外基质（ECM）在代谢性疾病背景下调节脂肪细胞代谢的作用尚不清楚。
本研究旨在确定与人类糖尿病（DM）相关的脂肪细胞代谢表型以及ECM在调节脂肪细胞代谢中的作用。
在标准二维（2D）细胞培养以及用人脂肪细胞重新填充的脱细胞脂肪组织ECM体外模型中研究肥胖患者的脂肪组织，并将结果与DM状态相关联。
本研究在学术大学医学中心和退伍军人管理局医院进行。
70例接受减肥手术的病态肥胖患者纳入研究。
在减肥手术时收集内脏和皮下脂肪组织。
本研究在2D细胞培养和三维ECM培养中对脂肪细胞的葡萄糖摄取、脂肪分解和脂肪生成进行代谢分析。
DM患者的脂肪细胞在2D培养中表现出葡萄糖摄取减少和脂肪分解减少。ECM支持成熟脂肪细胞的分化，并重现了在2D培养中观察到的脂肪细胞代谢中DM特异性差异。来自非DM患者的ECM部分挽救了DM患者脂肪细胞中的葡萄糖摄取和脂肪分解缺陷，而来自DM患者的ECM损害了非DM患者脂肪细胞中的葡萄糖摄取。
DM与脂肪细胞代谢功能障碍有关。ECM调节脂肪细胞代谢。非糖尿病ECM可挽救DM脂肪细胞中的代谢功能障碍，而DM ECM则赋予非糖尿病脂肪细胞代谢功能障碍特征。这些发现表明ECM是操纵脂肪组织代谢的一个靶点。
