Lumican modulates adipocyte function in obesity-associated type 2 diabetes

Obesity-associated type 2 diabetes (DM) leads to adipose tissue dysfunction. Lumican is a proteoglycan implicated in obesity, insulin resistance (IR), and adipocyte dysfunction. Using human visceral adipose tissue (VAT) from subjects with and without DM, we studied lumican effects on adipocyte function. Lumican was increased in VAT and adipocytes in DM. Lumican knockdown in adipocytes decreased lipolysis and improved adipogenesis and insulin sensitivity in VAT adipocytes in DM, while treatment with human recombinant lumican increased lipolysis and impaired insulin-sensitivity in an ERK-dependent manner. We demonstrate that lumican impairs adipocyte metabolism, partially via ERK signalling, and is a potential target for developing adipose tissue-targeted therapeutics in DM.

肥胖相关2型糖尿病（DM）可引发脂肪组织功能障碍。饰胶蛋白聚糖（Lumican）是一种与肥胖、胰岛素抵抗（IR）及脂肪细胞功能障碍相关的蛋白聚糖（proteoglycan）。本研究利用伴及不伴2型糖尿病受试者的人体内脏脂肪组织（VAT），探究饰胶蛋白聚糖对脂肪细胞功能的调控作用。研究结果显示，2型糖尿病患者的内脏脂肪组织及脂肪细胞中，饰胶蛋白聚糖的表达水平显著升高。在2型糖尿病患者的内脏脂肪组织脂肪细胞中，敲低饰胶蛋白聚糖的表达可抑制脂肪分解，同时改善脂肪生成能力与胰岛素敏感性；而经重组人饰胶蛋白聚糖处理脂肪细胞，则可增强脂肪分解并损伤胰岛素敏感性，且该效应呈细胞外信号调节激酶（ERK）依赖性。本研究证实，饰胶蛋白聚糖可部分通过ERK信号通路损害脂肪细胞代谢，其有望成为开发2型糖尿病脂肪组织靶向治疗药物的潜在靶点。