Elucidation of a novel relationship between the oxidative stress-related products and common diseases

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Adipocytokines such as adiponectin, leptin and resistin are hormone-like molecules that secreted from adipocytes. Recently oxidative stress has been reported to be associated to the abnormality of adipocytokine secretion, which evokes the metabolic syndrome. Previously we found that adipose CD36 functioning as a long-fatty acid transporter plays an role in clearance of oxidized low density lipoprotein (OxLDL) and advanced glycation end products (AGE)-modified molecules.In this study, we examined the effect of OxLDL and AGEs on adipocytekine secretions in 3T3-L1 adipose cells. First of all, both OxLDL and AGIE-BSA down-regulated the leptin expression via generation of active oxygen species. Second OxLDL up-regulated the plasminogen activator inhibitor-1 (PAI-1), which is a risk factor of atherosclerosis. We also demonstrated that lysophosphatidylcholine, which is a major phospholipids component of OxLDL, stimulates the PAI-1 mRNA expression via generation of ROS, resulting in an increasing of PAI-1 secretion. In addition, resistin, which evokes the insulin resistance, was up-regulated by the treatment of OxLDL on 3T3-L1 adipocytes. Polysome analysis revealed that OxLDL stimulated the protein translation of resistin mRNA. We also searched the major component of the resistin expression stimulator in OxLDL and found several fractions of the lipid peroxides.Consequent y we demonstrated that OxLDL stimulated the expression of both PAI-1 and resistin, and OxLDL and AGE-BSA reduced the expression of leptin. These results suggest oxidative stress-related products may alter the expression of adipocytokines, which involved n the metabolic syndromes. Further elucidation of the molecular mechanism by which OxLDL induces abnormality of adipocytokine secretion may shed light on a new aspect of metabolic syndromes and lead to the development of drug for the common diseases.