Background: Some experts believe that changes in gene expression may be a consequence of certain chemical exposures. Researchers are now focusing a lot of attention on the effects of these exposures on adipocytes which can produce inflammatory chemokines which may generate inflammation. It has been observed that some types of exposures are associated with obesity which is a risk factor for diabetes while, others can lead to weight reduction. Arsenescu demonstrated toxic exposures can stimulate and increase expansion of adipose tissue and other studies show alterations in the process of differentiation of preadipoctyes into adipocytes. In 2008, a preliminary study suggested endothelial dysfunction contributes to fat cell development because adipose stromal cells are in close contact with endothelial cells of capillaries and small blood vessels. (ScienceDaily) Long-term high serum levels of dioxin has been shown to contribute to endothelial dysfunction which provides a possible mechanism for the association of certain exposures to endothelial dysfunction, obesity and a higher risk for diabetes. (Peclova)
In the past, obesity has been characterized by differentiation of preadipocytes to adipocytes and involves the coordinated responses of a number of proteins with fatty acids that leads to increases of the size of fat cells.(Uto-Kondo) However, a recent study suggests that in in the case of abdominal obesity which may have more severe long-term health effects, there is impairment of the ability for preadipocytes to differentiate into adipocytes. Irakson says that "inhibition of this type can lead to a proinflammatory state and macrophage-like phenotype and as Hou explains "elevated levels of TNF-a or Il-1b in inflammatory tissues prolongs the survival of these immune cells and lengthens the durations they remain in an inflammatory state."
In one study, eldrin causes inhibition of a binding protein and interfered with expression of the anti-inflammatory protein PPAR-gamma and altered the expression of NF-kappaB which usually decreases as adipocytes differentiate. (Moreno-Aliego) We have suggested that the aberrant signaling from the AhR, which normally is important for cellular homeostasis and contributes to detoxification of PAHs and HAHS, may be an important factor in MCS. Hanlon et el notes that activation of the AhR by dioxin blocks hormone-induced adipocyte differentiation through the suppression of PPAR-gamma. The presence of inflammatory mediators are also associated with insulin resistance which can further impair normal cell function and reductions in the expression of Nrf2 may further complicate it. Chronic inflammation have been suggested as a causal factor in environmental illnesses including obesity and diabetes. One study shows proteins associated with cell death are less efficient in diffentiated adipocytes than in undifferentiated cells when introduced to a reactive species stimulus. Kojima confirmed an increase in antioxidants including MnSOD, catalase, Cu/ZnSOD as well as, FOXO with the the progression of adipocyte differentiation. From this study, it has been concluded that ROS-generated apoptosis is associated with the expression of FOXO3a in undifferentiated adipocytes and FOXO expression suppresses ROS-apoptosis through activation of scavenging enzymes in differentiated ones. With this study in mind and considering that uncontrolled production of ROS contribute to cellular processes that cause inflammation, preventing differentiation of adipocytes may have negative consequences in certain cases.
Kojima, T., Norose, T., Tsuchiya, K., and Sakamoto, K. Mouse 3t3-l1 cells acquire resistance against oxidative stress as the adipocytes differentiate via the transcription factor foxo. Apoptosis. http://www.citeulike.org/user/HEIRS/article/5998696
Isakson, P., Hammarstedt, A., Gustafson, B., and Smith, U. (2009). Impaired preadipocyte differentiation in human abdominal obesity. Diabetes, 58(7):1550-1557. http://www.citeulike.org/user/HEIRS/article/5017576
Hou, F. F., Boyce, J., Zhang, Y., and Owen, W. F. (2000). Phenotypic and functional characteristics of macrophage-like cells differentiated in pro-inflammatory cytokine-containing cultures. Immunology and cell biology, 78(3):205-213. http://www.citeulike.org/user/HEIRS/article/5998701
Hanlon, P. (2003). Ahr- and erk-dependent pathways function synergistically to mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin suppression of peroxisome proliferator-activated receptor-γ1 expression and subsequent adipocyte differentiation. Toxicology and Applied Pharmacology, 189(1):11-27. http://www.citeulike.org/user/HEIRS/article/5778106
Moreno-Aliaga, M. J. and Matsumura, F. (1999). Endrin inhibits adipocyte differentiation by selectively altering expression pattern of ccaat/enhancer binding protein-alpha in 3t3-l1 cells. Mol Pharmacol, 56(1):91-101. http://www.citeulike.org/user/HEIRS/article/5998840
Uto-Kondo, H., Ohmori, R., Kiyose, C., Kishimoto, Y., Saito, H., Igarashi, O., and Kondo, K. (2009). Tocotrienol suppresses adipocyte differentiation and akt phosphorylation in 3t3-l1 preadipocytes. J. Nutr., 139(1):51-57. http://www.citeulike.org/user/HEIRS/article/5998926
Healthy Blood Vessels May Prevent Fat Growth. ScienceDaily. September 23, 2008.
Pelclová, D., Prázny, M., Skrha, J., Fenclová, Z., Kalousová, M., Urban, P., Navrátil, T., Senholdová, Z., and Smerhovsky, Z. (2007). 2,3,7,8-tcdd exposure, endothelial dysfunction and impaired microvascular reactivity. Human & experimental toxicology, 26(9):705-713. http://www.citeulike.org/group/7254/article/6000451
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