The regulatory mechanism of the arachidonate cascade controlling the differentiation and quality changes in in adipocytes

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Adipocytes play a critical role in the control of the generation of obesity which is a well-known risk factor leading to the onset of life-style diseases. The obesity is characterized by the excess accumulation of fats through the increase in the number or the size of adipocytes. Recent studies suggested the involvement of the arachidoate cascade to generate eicosanoids, a group of lipid mediators, in the adipocytes and related cells. Some of these are effective to activate a nuclear receptor by acting as active ligands. In light of these advances, we planed to study the gene expression of the arachidonate cascade and the role of endogenous eicosanoids. We made use of mouse 3T3-L1 cells that can differentiate into the mature adipocytes in cell culture system to investigate the regulation of the expression of the arachidonate cyclooxygenase(COX) pathway leading to the formation of prostaglandin(PG)J_2 derivatives, which is a potent agonist of peroxisome proliferator-activated receptor γ in adipocytes. Through these studies, we clarified the specific gene expression patterns of isoforms of biosynthetic enzymes in the COX pathway. In addition, we found that distinct types of PGs were formed during the different stages of the life cycle of adipocytes. The related research led us to the specific roles of prostanoids in the apoptotic cell death and the differentiation of adipocytes. Moreover, we observed the effective actions of conjugated linolenic acid from bitter gourd seeds and abietic acid, a diterpene, as food-derived factors to regulate the life cycle of adipocytes. Separately, we identified the chemical structures of saponin derivatives generated during the food processing of horse chestnuts with wooden ashes, and were successful in finding anti-obese effects.