Melatonin inhibits fatty acid-induced triglyceride accumulation in ROS17/2.8 cells: implications for osteoblast differentiation and osteoporosis

Abstract

Melatonin is produced not only by the pineal gland but by cells of the bone marrow. Moreover, melatonin is known to promote osteogenic differentiation in several cell line models and in multipotential bone marrow mesenchymal stem cells. Fatty acids have been independently shown to direct such cells to acquire the phenotype and molecular characteristics of adipocytes. To examine the effect of melatonin on intracellular triglyceride accumulation, an indicator of adipogenic differentiation in the rat osteoblast-like ROS17/2.8 cell line, cells were incubated with added oleic acid (100 muM), fixed and stained with Oil Red O. Cellular lipid accumulation was quantitated by an Oil Red O method highly specific for triglycerides and expressed as a triglyceride accumulation index (TGAI, triglyceride per cell). Melatonin in nanomolar concentrations inhibited oleic acid-induced triglyceride accumulation. To identify the mechanism by which melatonin reduces triglyceride accumulation, cells were incubated with the two melatonin receptor antagonists, luzindole and S20928, or forskolin, a stimulator of adenylyl cyclase and cAMP production. These compounds prevented the inhibitory effect of melatonin on triglyceride accumulation, indicating that melatonin acts through known melatonin receptor-mediated mechanisms. In view of the previously demonstrated positive effects of melatonin in promoting osteoblastic differentiation in ROS17/2.8 cells and their reciprocal adipocytic differentiation induced by fatty acids, our observations may serve to relate the known age-related decreases of melatonin production, the shift in the bone marrow toward an adipocytic line of cell development, and the development of osteoporosis during aging.

Association study and expression analysis of MTNR1A as a candidate gene for body measurement and meat quality traits in Qinchuan cattle

“…In vitro studies involving the long-term melatonin treatment resulted in decreased expression of the glucose transporter GLUT4 and glucose uptake in adipocytes (Brydon et al, 2001). Furthermore, melatonin was reported to inhibit triglyceride accumulation in the rat osteoblast-like ROS17/2.8 cell line (Sanchez-Hidalgo et al, 2007). Due to the important role of melatonin in adipocyte biology, energy and lipid metabolism, it was treated as a potential therapeutic targets for obesity (She et al, 2009), and has been used to improve the production performance and meat quality of pig (Tang et al, 2006).…”

Melatonin as a potential therapeutic agent in psychiatric illness

“…This indoleamine is likely protective against oxidative damage in proliferating hematopoietic cells. Also, melatonin may be involved in bone development due to its influence on osteoblast differentiation (Acuña-Castroviejo, 2007;Radio et al, 2006;Sánchez-Hidalgo et al, 2007). Given these findings, the therapeutic treatment of depression using an SSRI in combination with melatonin may block the progressive bone loss resulting from the chronic use of SSRI.…”

“…It participates crucially in neurogenesis, immunomodulation (Srinivasan et al, 2008;Taupin, 2008), improving immune defense (Maldonado et al, 2007a(Maldonado et al, , 2007b, regulating circadian rhythms and sleep (Agez et al, 2009), eliminating free radicals (Peyrot and Ducroig, 2008;Reiter, 2003Reiter, , 2005aReiter, ,b, 2007Tan et al, 2007), intervening in lipid metabolism (Maldonado et al, 2006;Sánchez-Hidalgo et al, 2007), and also inhibiting cancer growth (Garcia-Navarro et al, 2007). Mechanistically, melatonin functions, in many cases, by acting through G-protein coupled membrane receptors, MT1 and MT2 (Garcia-Navarro et al, 2007;Maldonado et al, 2006;Sánchez-Hidalgo et al, 2007) and through nuclear receptors RZR/ROR (Paparrigopoulos et al, 2001). Melatonin production and rhythmicity exhibits marked variations (Macchi and Bruce, 2004).…”

“…Here, we hypothesized that melatonin may have important functions as an adjuvant therapy in mental disturbances due to its antiinflammatory, antinociceptive, anxiolytic, drug detoxification properties and its protective actions against osteoporosis, etc. (Maldonado et al, 2007a;Reiter et al, 2002;Sánchez-Hidalgo et al, 2007).…”

Age-related changes in melatonin synthesis in rat extrapineal tissues

“…Melatonin participates in diverse physiological functions and has great functional versatility related to the regulation of circadian rhythms and seasonal behaviour (Reiter, 1991), sexual development (Roy and Belsham, 2001), retinal physiology (Lundmark et al, 2006), osteogenesis (Sanchez-Hidalgo et al, 2007), tumour inhibition, antioxidant, anti-aging (Anisimov et al, 2006) and immunoenhancer properties (Guerrero and Reiter, 2002). More recently, it has been also implicated in bone homeostasis, cardiovascular, neurological and gastrointestinal systems (PandiPerumal et al, 2006).…”