Effects of arachidonic acid on the concentration of hydroxyeicosatetraenoic acids in culture media of mesenchymal stromal cells differentiating into adipocytes or osteoblasts

Abstract

Metabolites derived from the polyunsaturated fatty acids (PUFA) may modulate the mesenchymal stromal cell (MSC) differentiation. Such cells can differentiate into different cellular types, including adipocytes and osteoblasts. Aging favors the bone marrow MSC differentiation toward the former, causing a loss of bone density associated with pathologies like osteoporosis. The omega-6 arachidonic acid (AA) favors MSC adipogenesis to a greater extent than omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In this work, we study the joint action of both PUFA. Thus, not induced and induced to adipocyte or osteoblast MSC were treated with 20 lM of each PUFA (either AA, AA ? DHA or AA ? EPA). The expression of osteogenic and adipogenic molecular markers, the alox15b lipoxygenase gene expression and the 5-, 8-, 11-, 12-and 15-hydroxyeicosatetraenoic acids (HETE) derived from the AA metabolism in the culture media were determined. The results show that the adipogenesis induction of AA is not suppressed by the joint presence of EPA and DHA. In fact, both increased the adipogenic effect of AA on MSC differentiated into osteoblasts. The different HETE concentrations increased in cultures supplemented with AA, albeit such concentrations were lower in the cultures induced to differentiate, mainly at day 21 after the induction. Furthermore, the reduction in the HETE concentration was correlated with a higher expression of the alox15b gene. These results highlight the PUFA metabolism differences between uninduced and induced MSC to differentiate into adipocytes and osteoblasts, besides the relevant role of the lipoxygenase gene expression in adipogenesis induction.

Flaxseed oil ameliorated high-fat-diet-induced bone loss in rats by promoting osteoblastic function in rat primary osteoblasts

“…PA inhibited the expression of RUNX2 and osterix, and ALA reversed the inhibitory effect of PA in a concentration-dependent manner. However, Casado-Diaz et al showed that unsaturated fatty acids cannot reverse the inhibitory effect of omega-6 on osteogenesis [43]. The above study was inconsistent with the results of this study because of the different types of cells, intervention time, and application of omega-3 types.…”

Dietary ω-3 Fatty Acid Supplementation Improves Murine Sickle Cell Bone Disease and Reprograms Adipogenesis

“…The Western diet is abundant in ω-6 and deficient in ω-3, resulting in an abnormal ω 6/ω 3 ratio, which negatively impacts bone mass density [ 18 , 25 , 48 ]. Different studies have shown that ω-3 supplementation has a positive effect on bone mineral density and mineral content in human and moue models of bone loss [ 18 , 25 , 48 ]. In SCD mice, we previously showed that ω-3 diet supplementation (FD) normalizes cell ω 6/ω 3 ratios, reduces systemic inflammation and prevents H/R induced lung and kidney damage.…”

“…Two possible mechanisms have been invoked: reduction in osteoclast activity and/or increased osteoblast recruitment/activity [14,17]. It is worth noting that fatty acids have been suggested to be important in mesenchymal stem cell induction to adipogenesis, affecting bone health [18][19][20][21][22]. As osteoblast and adipocyte originate from a common precursor, a reduction in adipogenesis is required to ensure an adequate number of osteoblasts for bone formation.…”

Periparturient lipolysis and oxylipid biosynthesis in bovine adipose tissues

“…The increased content of 5-HETE in AT and plasma of cows at PP in the present study may be explained in part by the increased availability of both C16:0 and LA during PP because both FA promote the biosynthesis of 5-HETE by AT macrophages [ 42 ]. Given the angiogenic and adipogenic effects of 5-HETE [ 44 , 45 ], this metabolite may promote adequate AT remodeling during intense lipolysis, as both processes are necessary for inflammation resolution [ 4 ]. A third ArA metabolite that fluctuated in AT during the present study was 15-HETE.…”