Endocrine Abstracts

JOINT1308

Introduction: Bone marrow adipose tissue (BMAT) is a distinct and metabolically active fat depot within the bone marrow. BMAT negatively correlates with bone mineral density (BMD) and increases in diseases such as osteoporosis and type 2 diabetes. Surprisingly, BMAT also increases in caloric restriction (CR), a well-established intervention for enhancing metabolic health. Despite inducing widespread metabolic and endocrine adaptations, CR also promotes bone loss; however, the extent to which these changes are associated with BMAT remains unclear. This study aims to investigate the effects of CR duration on BMAT expansion, bone microarchitecture, and metabolic adaptations in male and female mice, providing further insights into the interplay of bone metabolism and systemic metabolic regulation during CR.

Method: Male and female mice were fed either ad libitum (AL) or a CR diet (70% of daily AL intake) for 1, 2, 4, or 6 weeks. Oral glucose tolerance tests (OGTT) and body composition analysis were conducted to evaluate metabolic responses. Serum levels of adiponectin, leptin, corticosterone, and insulin-like growth factor 1 (IGF-1) were measured at each time point. Bone microarchitecture and BMAT volume were analyzed using micro-computed tomography and osmium staining.

Results: The effects of CR on BMAT accumulation were region-specific: the primary effect was on the tibia, followed by the femur, while effects on the humerus were negligible. These effects on BMAT were also duration-dependent, with CR’s impact plateauing after 4 weeks of CR. Regarding bone microstructure, CR significantly decreased cortical bone area and thickness in both sexes but had a lesser influence on trabecular bone, decreasing only trabecular thickness in females. Notably, at the metaphysis, females exhibited greater CR-induced BMAT accumulation than males and this is accompanied by a reduction in trabecular thickness. CR improved glucose tolerance after only one week, and this effect persisted thereafter. During CR, adiponectin and corticosterone levels increased while leptin and IGF-1 levels declined. Notably, adiponectin levels plateaued around weeks 3–4 of CR, a pattern that coincided with BMAT expansion.

Conclusion: Our findings demonstrate that CR-induced BMAT expansion and bone architectural changes are influenced by CR duration, sex, and skeletal site. Moreover, the improvement in glucose tolerance observed with CR occurs independently of BMAT expansion, while BMAT accumulation may either contribute to or result from elevated adiponectin levels and cortical bone loss. Our findings highlight a potential interaction between BMAT and systemic metabolic adaptations.