Bone Marrow Adipose Tissue Regulation in the Setting of Calorie Restriction

Presentation Number: SH01-3
Date of Presentation: April 1st, 2017

Negin Misaghian*1, Maya Styner2 and Cody McGrath3
1UNC-CH, Chapel Hill, NC, 2University of North Carolina at Chapel Hill, Chapel Hill, NC, 3University of North Carolina at Chapel Hill

Abstract

Marrow Adipose Tissue (MAT) has been inversely correlated with bone quantity in post-menopausal osteoporosis and anorexia nervosa (1). This inverse relationship between MAT and bone has been attributed to preferential biasing of mesenchymal stem cells away from the osteogenic and toward the adipocytic lineage. Further, recent work showing increased MAT in the setting of preserved bone quantity (e.g. obesity) uncovers a complexity in the relationship between MAT and bone (2). It is likely that the MAT of anorexia/calorie restriction (CR) is phenotypically different from that of obesity. Herein, we aimed to ascertain MAT’s abundance, physiologic role and relevance to bone health in the setting of CR.

Nine-week old C57BL/6 female mice were fed a regular diet (RD) ad libum or a CR diet, which was consistent in terms micronutrients but contained 70% of total calories as compared to the RD mice. After 6 weeks, RD mice weighed 19.74 g ± 0.53 vs. CR, which weighed 14.94 g ± 0.53 (P <0.0001). We assessed bone microarchitecture via µCT: trabecular bone at the proximal tibial metaphysis was notably affected in CR: trabecular thickness was 27% lower in CR compared to RD (p= 0.0038) and there was a trend for lower trabecular BV/TV as well (13% lower, p=0.153). At the tibial mid-diaphysis, there was near-significance with regards to cortical area fraction BA/TA (9% lower in CR vs. RD, p-value=0.0573). Histologic analysis revealed a 400% increase in adipocyte # /HPF in the preliminary group of CR vs. RD sections analyzed (n=3 per group). Femoral MAT is currently being quantitatively assessed using MRI along with volumetric image analysis of the entire femur. This method has been validated and correlates to our volumetric assessment of marrow fat by osmium-µCT (3). Our preliminary results point to a robust finding of increased MAT in the setting of CR and our conclusive quantification with MRI as well as molecular analysis via qPCR will facilitate the understanding of this poorly understood fat depot. With this work, we aim to elucidate the physiologic role of MAT in the setting of CR and the extent to which this impacts bone health.

 

Nothing to Disclose: NM, MS, CM