DKFZ Junior Group Metabolism and Stem Cell Plasticity, German Cancer Research Center, Heidelberg, Germany.
DKFZ Junior Group Metabolism and Stem Cell Plasticity, German Cancer Research Center, Heidelberg, Germany.
Mol Metab. 2019 Jan;19:97-106. doi: 10.1016/j.molmet.2018.10.007. Epub 2018 Oct 23.
Extracellular matrix remodeling is required for adipose expansion under increased caloric intake. In turn, inhibited expandability due to aberrant collagen deposition promotes insulin resistance and progression towards the metabolic syndrome. An emerging role for the small leucine-rich proteoglycan Lumican in metabolically driven nonalcoholic fatty liver disease sparks an interest in further understanding its role in diet-induced obesity and metabolic complications.
Whole body ablation of Lumican (Lum) gene and adeno-associated virus-mediated over-expression were used in combination with control or high fat diet to assess energy balance, glucose homeostasis as well as adipose tissue health and remodeling.
Lumican was found to be particularly enriched in the stromal cells isolated from murine gonadal white adipose tissue. Likewise murine and human visceral fat showed a robust increase in Lumican as compared to fat from the subcutaneous depot. Lumican null female mice exhibited moderately increased fat mass, decreased insulin sensitivity and increased liver triglycerides in a diet-dependent manner. These changes coincided with inflammation in adipose tissue and no overt effects in adipose expandability, i.e. adipocyte formation and hypertrophy. Lumican over-expression in visceral fat and liver resulted in improved insulin sensitivity and glucose clearance.
These data indicate that Lumican may represent a functional link between the extracellular matrix, glucose homeostasis, and features of the metabolic syndrome.
在热量摄入增加的情况下，细胞外基质的重塑是脂肪扩张所必需的。反过来，由于胶原沉积异常导致的扩张能力受损，会促进胰岛素抵抗，并朝着代谢综合征的方向发展。小富含亮氨酸的蛋白聚糖 Lumican 在代谢驱动的非酒精性脂肪性肝病中的新作用激发了人们进一步了解其在饮食诱导的肥胖和代谢并发症中的作用的兴趣。
全身敲除 Lumican（Lum）基因，并结合对照或高脂肪饮食，使用腺相关病毒介导的过表达，以评估能量平衡、葡萄糖稳态以及脂肪组织的健康和重塑。
发现 Lumican 特别丰富于从鼠性腺白色脂肪组织中分离的基质细胞。同样，与皮下脂肪库相比，鼠和人内脏脂肪中的 Lumican 明显增加。Lumican 缺失的雌性小鼠表现出中等程度的脂肪量增加、胰岛素敏感性降低和肝甘油三酯增加，这与脂肪组织中的炎症和脂肪扩张能力（即脂肪细胞形成和肥大）没有明显变化有关。在内脏脂肪和肝脏中过表达 Lumican 可改善胰岛素敏感性和葡萄糖清除率。
这些数据表明，Lumican 可能是细胞外基质、葡萄糖稳态和代谢综合征特征之间的功能联系。
