Walji Tezin A, Turecamo Sarah E, Sanchez Alejandro Coca, Anthony Bryan A, Abou-Ezzi Grazia, Scheller Erica L, Link Daniel C, Mecham Robert P, Craft Clarissa S
Department of Cell Biology and Physiology, Washington University School of Medicine , St. Louis, MO , USA.
Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcala de Henares , Madrid , Spain.
Front Endocrinol (Lausanne). 2016 Jun 30;7:87. doi: 10.3389/fendo.2016.00087. eCollection 2016.
Marrow adipose tissue (MAT) is an endocrine organ with the potential to influence skeletal remodeling and hematopoiesis. Pathologic MAT expansion has been studied in the context of severe metabolic challenge, including caloric restriction, high fat diet feeding, and leptin deficiency. However, the rapid change in peripheral fat and glucose metabolism associated with these models impedes our ability to examine which metabolic parameters precede or coincide with MAT expansion. Microfibril-associated glycoprotein-1 (MAGP1) is a matricellular protein that influences cellular processes by tethering signaling molecules to extracellular matrix structures. MAGP1-deficient (Mfap2 (-/-)) mice display a progressive excess adiposity phenotype, which precedes insulin resistance and occurs without changes in caloric intake or ambulation. Mfap2 (-/-) mice were, therefore, used as a model to associate parameters of metabolic disease, bone remodeling, and hematopoiesis with MAT expansion. Marrow adiposity was normal in Mfap2 (-/-) mice until 6 months of age; however, by 10 months, marrow fat volume had increased fivefold relative to wild-type control at the same age. Increased gonadal fat pad mass and hyperglycemia were detectable in Mfap2 (-/-) mice by 2 months, but peaked by 6 months. The development of insulin resistance coincided with MAT expansion. Longitudinal characterization of bone mass demonstrated a disconnection in MAT volume and bone volume. Specifically, Mfap2 (-/-) mice had reduced trabecular bone volume by 2 months, but this phenotype did not progress with age or MAT expansion. Interestingly, MAT expansion in the 10-month-old Mfap2 (-/-) mice was associated with modest alterations in basal hematopoiesis, including a shift from granulopoiesis to B lymphopoiesis. Together, these findings indicate MAT expansion is coincident with insulin resistance, but not excess peripheral adiposity or hyperglycemia in Mfap2 (-/-) mice; and substantial MAT accumulation does not necessitate a proportional decrease in either bone mass or bone marrow cellularity.
骨髓脂肪组织（MAT）是一种内分泌器官，具有影响骨骼重塑和造血的潜力。病理性MAT扩张已在严重代谢挑战的背景下进行了研究，包括热量限制、高脂饮食喂养和瘦素缺乏。然而，与这些模型相关的外周脂肪和葡萄糖代谢的快速变化阻碍了我们检查哪些代谢参数先于MAT扩张或与之同时出现的能力。微原纤维相关糖蛋白1（MAGP1）是一种基质细胞蛋白，通过将信号分子连接到细胞外基质结构来影响细胞过程。MAGP1缺陷（Mfap2（-/-））小鼠表现出渐进性肥胖表型，该表型先于胰岛素抵抗出现，且在热量摄入或活动量无变化的情况下发生。因此，Mfap2（-/-）小鼠被用作将代谢疾病、骨重塑和造血参数与MAT扩张相关联的模型。Mfap2（-/-）小鼠在6个月龄之前骨髓脂肪正常；然而，到10个月时，骨髓脂肪体积相对于同年龄的野生型对照增加了五倍。Mfap2（-/-）小鼠在2个月时可检测到性腺脂肪垫质量增加和高血糖，但在6个月时达到峰值。胰岛素抵抗的发展与MAT扩张同时发生。骨量的纵向特征表明MAT体积与骨体积之间存在脱节。具体而言，Mfap2（-/-）小鼠在2个月时小梁骨体积减少，但这种表型并未随年龄增长或MAT扩张而进展。有趣的是，10个月大的Mfap2（-/-）小鼠的MAT扩张与基础造血的适度改变有关，包括从粒细胞生成向B淋巴细胞生成的转变。总之，这些发现表明，在Mfap2（-/-）小鼠中，MAT扩张与胰岛素抵抗同时发生，但与外周脂肪过多或高血糖无关；大量的MAT积累并不一定需要骨量或骨髓细胞数量成比例减少。
