Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes

Abstract

Fat occupies a significant portion of bone cavity however its function is largely unknown. Marrow fat expands during aging and in conditions which affect energy metabolism, indicating that fat in bone is under similar regulatory mechanisms as other fat depots. On the other hand, its location may determine specific functions in the maintenance of the environment for bone remodeling and hematopoiesis. We have demonstrated that marrow fat has a distinctive phenotype, which resembles both, white and brown adipose tissue (WAT and BAT, respectively). Marrow adipocytes express gene markers of brown adipocytes at levels characteristic for the BAT, including transcription factor Prdm16, and regulators of thermogenesis such as deiodinase 2 (Dio2) and PGC1α. The levels of expression of BAT-specific gene markers are decreased in bone of 24 mo old C57BL/6 and in diabetic yellow agouti Avy/a mice implicating functional changes of marrow fat occurring with aging and diabetes. Administration of antidiabetic TZD rosiglitazone, which sensitizes cells to insulin and increases adipocyte metabolic functions, significantly increased both, BAT (UCP1, PGC1α, Dio2, β3AR, Prdm16, and FoxC2) and WAT (adiponectin and leptin) gene expression in marrow of normoglycemic C57BL/6 mice, but failed to increase the expression of BAT, but not WAT, gene markers in diabetic mice. In conclusion, the metabolic phenotype of marrow fat combines both BAT and WAT characteristics. Decrease in BAT-like characteristics with aging and diabetes may contribute to the negative changes in the marrow environment supporting bone remodeling and hematopoiesis.

Brown adipose tissue and bone

“…36,37 Recently, it was shown that MAT has a distinct phenotype resembling both WAT and BAT. 38 The authors showed that MAT expresses several BAT-selective genes including Prdm16, Dio2 and Pgc1α at similar levels as in the interscapular BAT depot. However, the expression level of the thermogenic effector gene Ucp1 was very low, possibly due to the presence of unstimulated beige or beige-like adipocytes in the MAT.…”

Adipogenesis: new insights into brown adipose tissue differentiation

“…Nishio et al (2012) developed an alternative approach to reprogram hES and IPS cells into functional brown adipocytes both in vitro and in vivo with an efficiency of O90% without utilizing exogenous gene transfer. The protocol was initially discovered by observations that conditions which were established to differentiate cells of the haematopoietic lineage resulted in the production of significant numbers of brown adipocytes (Thorns et al 2008, Krings et al 2012. They employed a haemopoietic cocktail (HC) composed of KIT ligand (KITGL), fms-related tyrosine kinase 3 ligand (FLT3LG), interleukin 6 (IL6), and VEGF along with the previously reported BAT inducer BMP7 (Tseng et al 2008).…”

In Osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis

“…Later, these cells have been proposed to have a role as an energy source, or as modulators of adjacent tissue by the production of paracrine, and autocrine factors (reviewed in Rosen et al, 2009). In fact, adipokines, steroids, and cytokines (Lee et al, 2002;Pino et al, 2010;Rosen et al, 2009;) can exert profound eff ects on neighboring marrow cells, sustaining or suppressing hematopoietic and osteogenic processes (Omatsu et al, 2010;Krings et al, 2012;Rosen et al, 2009;Rodríguez et al, 2008). Thus, the function of bone marrow adipose tissue may be similar to that of extra medullary fat.…”