Altered Metabolomics and Inflammatory Transcriptomics in Human Bone Marrow Adipocytes After Acute High Calorie Diet and Acute Fasting

Expansion of bone marrow adipocytes has been linked to nutritional pressures, suggesting that bone marrow is a dynamic compartment that responds to fluctuations in systemic nutritional availability to regulate osteogenesis and hematopoiesis. Here we investigated bone marrow metabolism in response to acute overnutrition (high calorie diet) and calorie deprivation (fasting). Participants underwent a 10-day high calorie diet followed by a two-week interval of an ad libitum diet and then underwent 10 days of fasting. Bone marrow adipocytes were collected before and after each dietary intervention. Using RNA-sequencing, we characterized nutritional influences on bone marrow adiposity. Bone marrow adipocytes after high calorie diet showed an upregulation of FOXP3 (p < 0.0001), the transcription factor that controls the development of Tregs, which are critical in reducing inflammatory immune responses. In contrast, bone marrow adipocytes after acute fasting had an upregulation of inflammatory genes (CP, CFH, and IGFBP3) (p < 0.0001). Overall, our results demonstrate key differences in inflammatory responses between high calorie diet and fasting, despite a nearly identical phenotype of bone marrow adipose tissue expansion. Further analyses are needed to understand the effects nutritional pressures have on bone marrow adipogenesis and immune responses. RNA-sequencing of bone marrow adipocytes before (pre) and after (post) acute high calorie diet and acute fasting. P-values were determined based on the comparison of the post to pre groups; high calorie post:pre (high nutritional effect) and fasting post:pre (low nutritional effect).