Drenka Trivanović1*, Jovana Kovačević2, Aleksandra Arsić1, Marko Vujačić3, Nikola Bogosavljević3, Ivana Okić Djordjević1, Milena Živanović1, Slavko Mojsilović1, Mirjana Maljković2, and Aleksandra Jauković1
1Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr. Subotića 4, 11000 Belgrade, Serbia
2Faculty of Mathematics, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia
3Institute for Orthopedy Banjica, Mihaila Avramovića 28, 11000, Belgrade, Serbia
drenka.trivanovic [at] imi.bg.ac.rs
Abstract
As adipose tissue (AT) undergoes metabolic reprogramming with age, we investigated skeletal site-specific and age-dependent lipid profile of bone marrow adipose tissue (BMAT).
Acetabular and femoral BMAT, and gluteofemoral subcutaneous adipose tissue (gfSAT) were obtained from matched osteoarthritis patients. Patients were classified into two groups: younger (≤ 60 years) and aged (>60 years) adults. BMAT and gfSAT were explored by using thin layer/gas chromatography coupled with cellular and molecular assays. Data were interpreted and visualized by applying linear discriminant analysis (LDA) and hierarchical clustering of fatty acid (FA) composition. Statistics was estimated by non-parametric tests and Spearman’s rank correlation.
Analyses of total lipids revealed significantly reduced triglyceride content in femoral (fBMAT) than in acetabular BMAT (aBMAT) and gfSAT. Frequencies of spontaneously released saturated palmitic (C16:0) and stearic acids (C18:0) were higher in fBMAT than in aBMAT and gfSAT (p=0.036 and p=0.046, n=8). Cluster heatmap and LDA showed that fBMAT differed to acetabular and gfSAT, while acetabular and gfSAT were more similar in FA profiles. FA profiles of AT depots varied with patient’s age. Contribution of palmitic acid was increased in aged group in all AT depots, while stearic acid declined in aged group in BMAT compartments only. fBMAT cellularity declined with age (r=-0.675, n=14, p=0.037). Additionally, the presence of CD45-CD31-CD34+CD24+ adipogenic progenitor (stem) cells was increased in fBMAT (0.46±0.03%) when compared to aBMAT (0.21±0.01%) depot. Femoral mesenchymal stem cells displayed pronounced adipogenesis comparing to their acetabular counterparts.
Our findings suggest that specific lipid profile of fBMAT imposes adipogenic commitment of stem cells within this skeletal site.
Keywords: bone marrow adipose tissue, fatty acids, stem cells, adipogenesis, aging
Acknowledgement: Work is supported by the Ministry of Education, Science and Technological Development of Republic of Serbia [contract number 451–03-68/2022–14/200015 with Institute for Medical Research University of Belgrade, National Institute of Republic of Serbia]
