AUTHOR=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. 

TITLE=Marrow Adipose Tissue Expansion Coincides with Insulin Resistance in MAGP1-Deficient Mice

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 7 - 2016

YEAR=2016

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2016.00087

DOI=10.3389/fendo.2016.00087

ISSN=1664-2392

ABSTRACT=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 (ECM) 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 5-fold relative to WT 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.