Transcriptomic analysis of bone marrow adipose tissue reveals enrichment in lipid transport in response to a Western...

Bone marrow adipose tissue (BMAT) is now recognized as a functional fat depot distinct from extramedullary white and brown adipose tissues (WAT and BAT, respectively). BMAT expands in metabolic disorders such as obesity. However, the mechanism by which BMAT expands is less clear. Here, we present a comparative analysis of the transcriptomes of BMAT, WAT, and BAT from 20-week-old Sprague-Dawley rats fed a chow diet (12% kJ fat) using bulk RNA sequencing (RNA-seq). Gene-set enrichment analysis revealed overrepresentation of transcripts related to cellular proliferation and the population of adipoprogenitor cells in BMAT. To further study BMAT expansion, we introduced a 12-week dietary intervention of a Western diet (42% kJ fat). We first characterized obesity-related phenotypes such as adipocyte hypertrophy. Then, we compared the transcriptomes of femoral and tibial BMAT or gonadal WAT to the chow group. Western diet significantly increased body weight (P = .02), whole-body fat percentage (P = .009), adipocyte size in humeral BMAT (P = .02), and gonadal WAT (P = .005) compared with the chow group. BMAT had a more robust transcriptomic response to the Western diet than WAT. The transcriptome of BMAT was enriched in pathways related to lipid transport. In WAT, this enrichment was more related to lipid biosynthesis and modification. In summary, our data may suggest differences in the developmental maturity of BMAT relative to WAT and BAT in the chow group. A Western diet induces differential responses in the transcriptomes of BMAT and WAT related to lipid homeostasis. In BMAT, enrichment in the lipid transport pathways on the Western diet may suggest a role for BMAT in nutrient sensing and lipid uptake.