Obesity is a medical condition as abnormal or excessive fat accumulation. Obesity is a potential risk factor causing various diseases, such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. In 2005, the WHO estimates that at least 400 million adults (9.8%) are obese, with higher rates among women than men. Vitamin A was recognized as an essential factor in embryonic development, vision, tissue remodeling, and immune function. Vitamin A in blood first binds to serum retinol binding protein (RBP) and then is transported into cells by a membrane protein, stimulated by retinoic acid 6(STRA6). Previous study showed that blood levels of RBP are increased in obese rodents and humans, and the increased level of RBP leads to insulin resistance.therefore, vitamin A is considered ro involve in lipid metabolism and insulin responses. Recent experiments indicated that STRA6 is not only a vitamin A transporter but also functions as a surface signaling receptor, which can bind to RBP to activate the downstream cascade. Berry et al. discovered that association of retinol-bound RBP with the vitamin A transporter STRA6 is mediated by the Janus kinase JAK2 and STATs, which results in upregulation of genes that inhibit insulin signaling and that control lipid homeostasis[1]. However, It also has been reported that administration of RBP to mice results in upregulation of expression of hepatic PEPCK. As the liver does not express STRA6, this implies the existence of other mechanisms resulting from induction of insulin resistance by RBP. However, though surgery is carried out, the 5-year survival only increases to 21%. It is reported previously that interferon (IFN)- in combination with adjuvant chemoradiotherapy improved 5-year survival to 55%. Subsequently, another member of IFNs, IFN-is found to present an in vitro antitumor activity stronger than IFN- in tumors of the pancreas and in adrenal cancer via inducing cell cycle arrest and apoptosis activation. Pancreatic cancer refers to a malignant neoplasm of the pancreas. 85% of all cancerous tumors of the pancreas are adenocarcinomas. Pancreatic cancer is the fourth leading cause of cancer deaths among people in the worldwide. The relative 1-year survival rate for pancreatic cancer is only 24%, and the overall 5-year survival is 5%. Surgery remains the only curative therapy. The peroxisome proliferator-activated receptor (PPAR-) is considered as the main target of the insulin sensitizing drugs, such as troglitazone (TGZ), and integrates the control of energy, lipid, and glucose homeostasis. PPAR- agonists display antineoplastic effects in pancreatic cancer by function as negative modulators of STAT-3[1]. Recently, Vitale et al. reported the combination between IFN- and TGZ in pancreatic cancer. In order to evaluate molecular mechanisms causing the synergistic antitumor activity of IFN- and PPAR- agonists, they found stronger effects on STAT protein expression and activationin in combination of IFN- and PPAR- than in alone. Further study suggest that single agents could induce MAPK and AKT expression and activation due to resistance, but these effects were antagonized by the combined treatment. In summary, though many questions remain to be confirmed, vitamin A circulation may be a important target in obesity treatment via JAK/STAT signaling pathway. Reference [1]. Biochim. Biophys. Acta (2011), doi:10.1016/j.bbalip.2011.07.002 Related Post Potential effects of AOPPs against atherosclerosis via JAK/STAT signaling pathway
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