Title of project

Molecular Phenotyping of Dietary-Induced Bone Marrow Adipocytes in Mice

Abstract

Obesity is a global health problem, and understanding the roles of specific fat tissue depots helps in assessing metabolic health, shaping lifestyle recommendations, and improving treatment regimes. Adipocytes within the bone are unique, as expansion is not only observed in obese subjects but conversely also during calorie deficiency. The expansion of marrow adipose tissue has been postulated to be due to a lineage shift of bone residing progenitor cells from osteoblast to adipocytes since marrow adipose tissue is elevated in conditions with low bone mass or increased fracture risk.

But since marrow adipose tissue expansion has been documented in subjects with osteoporosis, type I diabetes, obesity, and anorexia nervosa, as well as people suffering from skeletal unloading and radiation exposure, I hypothesize that bone marrow adipocytes obtain a context specific phenotype and role in bone homeostasis that goes beyond a simple lineage shift. To test this, I propose a multidisciplinary approach to determine molecular, spatial, and time dependent phenotypes of bone marrow adipocytes in mice undergoing dietary interventions. We will expose mice to alternating schemes of high fat diet and caloric restriction and use contrast enhanced μCT and single nuclei RNA-sequencing to characterize anatomical and molecular properties of expanding bone marrow adipocytes in the context of bone microarchitecture and strength. My findings about the context specific relationship between marrow adipocyte function and bone integrity will eventually advance the clinical management of a variety of bone diseases through targeting and monitoring of marrow adipocyte content in a personalized manner to support overall bone homeostasis and regeneration.