Mechanisms of palmitate-induced lipotoxicity in osteocytes
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Fecha
2019-06
Autores
Al Saedi, Ahmed
Bermeo, Sandra
Plotkin, Lilian
Myers, Damian E.
Duque, Gustavo
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Editor
Elsevier
Resumen
Background: Lipotoxicity is defined as cellular toxicity observed in the presence of an abnormal accumulation of
fat and adipocyte-derived factors in non-fat tissues. Palmitic acid (PA), an abundant fatty acid in the bone
marrow and particularly in osteoporotic bones, affects osteoblastogenesis and osteoblast function, decreasing
their survival through induction of apoptosis and dysfunctional autophagy. In this study, we hypothesized that
PA also has a lipotoxic effect on osteocytes in vitro.
Methods: Initially, we tested the effect of PA on osteocyte-derived factors DKK1, sclerostin and RANKL. Then, we
tested whether PA affects survival and causes apoptosis in osteocytes. Subsequently, we investigated the effect of
PA on autophagy by detecting the membrane component LC3-II (Western blot) and staining them and lysosomes
with Lysotracker Red dye.
Results: PA decreases RANKL, DKK1 and sclerostin expression in osteocytes. In addition, we found that PA
induces apoptosis and reduces osteocyte survival. PA also caused autophagy failure identified by a significant
increase in LC3-II and a reduced number of autophagosomes/lysosomes in the cytoplasm.
Conclusion: In addition to the effects of PA on RANKL, DKK1 and sclerostin expression, which could have significant
deleterious impact on bone cell coupling and bone turnover, PA also induced apoptosis and reduced
autophagy in osteocytes. Considering that apoptosis and cell dysfunction are two common changes occurring in
the osteocytes of osteoporotic bone, our findings suggest that PA could play a role in the pathogenesis of the
disease. Suppression of these effects could bring new potential targets for therapeutic interventions in the future.
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Palabras clave
Palmitic acid, Osteocytes, Lipotoxicity, Fatty acids, Osteoporosis, Apoptosis, Autophagy