Oleate Abrogates Palmitate-Induced Lipotoxicity and Proinflammatory Response in Human Bone Marrow-Derived Mesenchymal Stem Cells and Osteoblastic Cells.
Osteoporosis is a metabolic bone disease associated with unequilibrated bone remodeling resulting from decreased bone formation and/or increased bone resorption, leading to progressive bone loss. In osteoporotic patients, low bone mass is associated with an increase of bone marrow fat resulting from accumulation of adipocytes within the bone marrow. Marrow adipocytes are active secretory cells, releasing cytokines, adipokines and free fatty acids (FA) that influence the bone marrow microenvironment and alter the biology of neighboring cells. Therefore, we examined the effect of palmitate (Palm) and oleate (Ole), 2 highly prevalent FA in human organism and diet, on the function and survival of human mesenchymal stem cells (MSC) and MSC-derived osteoblastic cells. The saturated FA Palm exerted a cytotoxic action via initiation of endoplasmic reticulum stress and activation of the nuclear factor κB (NF-κB) and ERK pathways. In addition, Palm induced a proinflammatory response, as determined by the up-regulation of Toll-like receptor 4 expression as well as the increase of IL-6 and IL-8 expression and secretion. Moreover, we showed that MSC-derived osteoblastic cells were more sensitive to lipotoxicity than undifferentiated MSC. The monounsaturated FA Ole fully neutralized Palm-induced lipotoxicity by impairing activation of the pathways triggered by the saturated FA. Moreover, Ole promoted Palm detoxification by fostering its esterification into triglycerides and storage in lipid droplets. Altogether, our data showed that physiological concentrations of Palm and Ole differently modulated cell death and function in bone cells. We therefore propose that FA could influence skeletal health.
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Gillet
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Spruyt
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Rigutto
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Dalla Valle
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Berlier
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Louis
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Debier
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Gaspard
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Malaisse
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Gangji
Laboratory of Bone and Metabolic Biochemistry (C.G., D.S., S.R., A.D.V., J.B., N.G., W.J.M., V.G., J.R.), Faculty of Medicine, Université libre de Bruxelles, B-1070 Brussels, Belgium; Institute of Life Sciences (C.L., C.D.), Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium; and Department of Rheumatology and Physical Medicine (V.G.), Erasme Hospital, B-1070 Brussels, Belgium.
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Rasschaert
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D010168:Palmitates; D051197:Toll-Like Receptor 4; D019301:Oleic Acid; D048049:Extracellular Signal-Regulated MAP Kinases