Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
BioTechMed-Graz, Graz, Austria.
Exp Clin Endocrinol Diabetes. 2023 Dec;131(12):639-645. doi: 10.1055/a-2192-0101. Epub 2023 Nov 13.
As a result of an unhealthy diet and limited physical activity, obesity has become a widespread pandemic worldwide and is an important predictor for the development of cardiovascular disease. Obesity is often characterized by a pro-inflammatory environment in white adipose tissue (WAT), mainly due to increased macrophage infiltration. These immune cells boost their lipid concentrations by accumulating the content of dying adipocytes. As the lysosome is highly involved in lipid handling, the progressive lipid accumulation may result in lysosomal stress and a metabolic shift. Recent studies have identified glycoprotein non-metastatic melanoma protein B (GPNMB) as a novel marker of inflammatory diseases. GPNMB is a type I transmembrane protein on the cell surface of various cell types, such as macrophages, dendritic cells, osteoblasts, and microglia, from which it can be proteolytically cleaved into a soluble molecule. It is induced by lysosomal stress via microphthalmia-associated transcription factor and thus has been found to be upregulated in many lysosomal storage disorders. In addition, a clear connection between GPNMB and obesity was recently established. GPNMB was shown to have protective and anti-inflammatory effects in most cases, preventing the progression of obesity-related metabolic disorders. In contrast, soluble GPNMB likely has the opposite effect and promotes lipogenesis in WAT. This review aims to summarize and clarify the role of GPNMB in the progression of obesity and to highlight its potential use as a biomarker for lipid-associated disorders.
由于不健康的饮食和有限的身体活动，肥胖已成为全球范围内广泛流行的疾病，并且是心血管疾病发展的重要预测指标。肥胖症通常以白色脂肪组织（WAT）中的促炎环境为特征，主要是由于巨噬细胞浸润增加。这些免疫细胞通过积累死亡脂肪细胞的内容物来增加它们的脂质浓度。由于溶酶体高度参与脂质处理，渐进性脂质积累可能导致溶酶体应激和代谢转变。最近的研究已经确定糖蛋白非转移性黑色素瘤蛋白 B（GPNMB）是炎症性疾病的新型标志物。GPNMB 是各种细胞类型（如巨噬细胞、树突状细胞、成骨细胞和小神经胶质细胞）表面的 I 型跨膜蛋白，可通过蛋白水解作用将其切割成可溶性分子。它通过小眼相关转录因子诱导溶酶体应激，因此在许多溶酶体贮积病中发现其上调。此外，最近还发现了 GPNMB 与肥胖之间的明确联系。GPNMB 在大多数情况下具有保护和抗炎作用，可防止肥胖相关代谢紊乱的进展。相比之下，可溶性 GPNMB 可能具有相反的作用，并促进 WAT 中的脂肪生成。本综述旨在总结和阐明 GPNMB 在肥胖进展中的作用，并强调其作为与脂质相关疾病的生物标志物的潜在用途。
