Analysis of fatty acid composition in human bone marrow aspirates

Deshimaru, Ryota; Ishitani, Ken; Makita, Kazuya; Horiguchi, Fumi; Nozawa, Shiro

doi:10.2302/kjm.54.150

Cited by 15 publications

(14 citation statements)

References 28 publications

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“…We found that palmitate and stearate are not only the predominant FA present in the lipotoxic media but also that these two FA significantly affect osteoblast function and survival. Interestingly, these two FA have been shown not only to have a toxic effect on several cell types including hepatocytes [26], beta cells [27] and osteoblasts [30], but also in the particular case of palmitate, it has been reported as one of the most prevalent FA secreted into the bone marrow [31] as well as a potent inducer of apoptosis in osteoblasts [20]. In agreement with previous studies looking at lipotoxicity in other cell models [20, 26], both, palmitate and stearate showed a lipotoxic effect in our model through the induction of apoptotic changes and the activation of caspases 3/7.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

Elbaz

Rivas

et al. 2010

J Cellular Molecular Medi

151

104

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Although increased bone marrow fat in age-related bone loss has been associated with lower trabecular mass, the underlying mechanism responsible remains unknown. We suggested that marrow adipocytes exert a lipotoxic effect on osteoblast function and survival through the reversible biosynthesis of fatty acids (FA) into the bone marrow microenvironment. We have used a two-chamber system to co-culture normal human osteoblasts (NHOst) with differentiating pre-adipocytes in the absence or presence of an inhibitor of FA synthase (cerulenin) and separated by an insert that allowed unidirectional trafficking of soluble factors only and prevented direct cell–cell contact. Supernatants were assayed for the presence of FA using mass spectophotometry. After 3 weeks in co-culture, NHOst showed significantly lower levels of differentiation and function based on lower mineralization and expression of alkaline phosphatase, osterix, osteocalcin and Runx2. In addition, NHOst survival was affected by the presence of adipocytes as determined by MTS-formazan and TUNEL assays as well as higher activation of caspases 3/7. These toxic effects were inhibited by addition of cerulenin. Furthermore, culture of NHOst with either adipocyte-conditioned media alone in the absence of adipocytes themselves or with the addition of the most predominant FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear binding was affected by addition of either adipocyte conditioned media or FA into the osteogenic media. We conclude that the presence of FA within the marrow milieu can contribute to the age-related changes in bone mass and can be prevented by the inhibition of FA synthase.

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Section: Discussionmentioning

confidence: 99%

Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

Elbaz

Rivas

et al. 2010

J Cellular Molecular Medi

151

104

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“…Also, oleic acid but not palmitic acid, increases the rate of alkaline phosphatase positive ST2 cells induced by bone morphogenetic protein-2 [31]. It has been proposed that all these differences may affect osteoblast differentiation in the bone marrow microenvironment [31]. However, the effects of phospholipid fatty acids on osteoblast differentiation are not yet fully understood.…”

Section: Importance Of Dietary Fatty Acids On Phospholipid Distributimentioning

confidence: 99%

Nutritional Deficiencies and Phospholipid Metabolism

Giménez

Oliveros

Gómez

2011

IJMS

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Phospholipids are important components of the cell membranes of all living species. They contribute to the physicochemical properties of the membrane and thus influence the conformation and function of membrane-bound proteins, such as receptors, ion channels, and transporters and also influence cell function by serving as precursors for prostaglandins and other signaling molecules and modulating gene expression through the transcription activation. The components of the diet are determinant for cell functionality. In this review, the effects of macro and micronutrients deficiency on the quality, quantity and metabolism of different phospholipids and their distribution in cells of different organs is presented. Alterations in the amount of both saturated and polyunsaturated fatty acids, vitamins A, E and folate, and other micronutrients, such as zinc and magnesium, are discussed. In all cases we observe alterations in the pattern of phospholipids, the more affected ones being phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. The deficiency of certain nutrients, such as essential fatty acids, fat-soluble vitamins and some metals may contribute to a variety of diseases that can be irreversible even after replacement with normal amount of the nutrients. Usually, the sequelae are more important when the deficiency is present at an early age.

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“…; 3) In certain cases of leukemia, a shift of low density lipoprotein (LDL) from blood to spleen, liver and bone marrow was observed [14]–[15]. At the remission, LDL in peripheral blood return to normal values.A drop in saturated and monounsaturated fatty acids in the bone marrow was also described in leukemic patient [16], [17]. The involvement of fatty acids has been widely demonstrated in some cancers such as breast cancer [18]–[19] but has never been studied in CML.…”

Section: Introductionmentioning

confidence: 99%

Leptin Reverts Pro-Apoptotic and Antiproliferative Effects of α-Linolenic Acids in BCR-ABL Positive Leukemic Cells: Involvement of PI3K Pathway

et al. 2011

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It is suspected that bone marrow (BM) microenvironmental factors may influence the evolution of chronic myeloid leukaemia (CML). In this study, we postulated that adipocytes and lipids could be involved in the progression of CML. To test this hypothesis, adipocytes were co-cultured with two BCR-ABL positive cell lines (PCMDS and K562). T cell (Jurkat) and stroma cell (HS-5) lines were used as controls. In the second set of experiments, leukemic cell lines were treated with stearic, oleic, linoleic or α-linolenic acids in presence or absence of leptin. Survival, proliferation, leptin production, OB-R isoforms (OB-Ra and OB-Rb), phosphoinositide 3-kinase (PI3k) and BCL-2 expression have been tested after 24h, 48h and 72h of treatment. Our results showed that adipocytes induced a decrease of CML proliferation and an increase in lipid accumulation in leukemic cells. In addition, CML cell lines induced adipocytes cell death. Chromatography analysis showed that BM microenvironment cells were full of saturated (SFA) and monounsaturated (MUFA) fatty acids, fatty acids that protect tumor cells against external agents. Stearic acid increased Bcl-2 expression in PCMDS, whereas oleic and linoleic acids had no effects. In contrast, α-linolenic acid decreased the proliferation and the survival of CML cell lines as well as BCL-2 and OB-R expression. The effect of α-linolenic acids seemed to be due to PI3K pathway and Bcl-2 inhibition. Leptin production was detected in the co-culture medium. In the presence of leptin, the effect of α-linolenic acid on proliferation, survival, OB-R and BCl-2 expression was reduced.

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Analysis of fatty acid composition in human bone marrow aspirates

Cited by 15 publications

References 28 publications

Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

Nutritional Deficiencies and Phospholipid Metabolism

Leptin Reverts Pro-Apoptotic and Antiproliferative Effects of α-Linolenic Acids in BCR-ABL Positive Leukemic Cells: Involvement of PI3K Pathway

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