Control of life cycle of mouse adipogenic 3T3-L1 cells by dietary lipids and metabolic factors

Adipocytes function not only as in the storage and mobilization of lipids but also as endocrine cells by secreting tumor necrosis factor-α (TNF-α), free fatty acids, and other cytokines. To study the effects of dietary lipids and metabolic factors on the control of the life cycle of adipocytes, we utilized mouse 3T3-L1 preadipocytes that could be induced to differentiate into adipocytes. To evaluate the role of endogenous prostaglandins (PGs) in the adipogenic changes, we examined the effect of specific inhibitors of cyclooxygenase (COX). SC-560, a specific COX-1 inhibitor, suppressed adipogenesis dose dependently, suggesting a role of constitutive COX-1 in the endogenous synthesis of PGs, including PGJ₂ derivatives formed by mature adipocytes with the ability to promote adipogenesis. NS-398, a COX-2 inhibitor, had little influence on the maturation processes. Both COX inhibitors were effective in stimulating apoptosis of preadipocytes induced by TNF-α, indicating that both PGE₂ and PGF_2α produced by preadipocytes through the action of both COX isoforms serve as survival factors. However, the effect of both inhibitors was negligible for the proliferation of preadipocytes. Moreover, conjugated linolenic acid from bitter gourd at lower concentrations that was without effects by itself synergistically stimulated TNF-α-induced apoptosis. Therefore, dietary lipid factors are capable of controlling the life cycle of adipocytes together with metabolic factors.     

Regulation and role of arachidonate cascade during changes in life cycle of adipocytes

Although some eicosanoids serve as potent natural ligands to activate peroxisome proliferator-activated receptor (PPARγ), the ability of adipocytes to produce eicosanoids and regulate PPARγ remains unclear. Here, adipogenic 3T3-L1 cells were employed to determine the gene expression of isoforms of biosynthetic enzymes in the arachidonate cyclooxygenase (COX) pathway and the synthesis of prostaglandins (PGs). The expression of COX-2 was induced transiently in a biphasic manner upon the triggering of the differentiation and maturation phases while COX-1 was constitutive. The exclusive expression of lipocalin-type PGD synthase occurred and gradually increased during the maturation process along with the stable expression of PPARγ. Moreover, we confirmed the formation of PGD₂ from arachidonic acid by the mature adipocytes, suggesting conversion into PGJ₂ derivatives. Even though cytosolic and membrane-associated subtypes of PGE synthase were expressed at relatively constant levels, the ability of preadipocytes to produce PGE₂ was greater than that of mature adipocytes in the cell response. The treatment of the mature adipocytes with exogenous PGD₂, 15-deoxy-Δ^12,14-PGJ₂ and PGE₂, in the presence of aspirin, enhanced the adipogenesis. These findings imply the specific roles of prostanoids produced by the mature adipocytes in the maintenance of terminal differentiation through an autocrine control mechanism.     

Synthesis of 20S-protopanaxadiol 20-O-β-D-glucopyranoside, a metabolite of Panax ginseng glycosides, and compounds related to it

A preparative semi-synthetic method was developed to prepare 20S-protopanaxadiol 20-O-β-Dglucopyranoside (1), a metabolite of Panax ginseng glycosides. The 20-O-•-D-glucopyranosides of 20S-hydroxydammar-24-en-3,12-dione, 3β,20S-dihydroxydammar-24-en-12-one, and 3β,12α, 20S-trihydroxydammar-24-ene were synthesized for the first time. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 364–369, July–August, 2006.     

Two new benzoyl esters of glucose from Lagotis yunnanensis

Two new benzoyl esters of glucose 1-O-(E)-4′-methoxybenzoyl-β-D-glucopyranose (1) and 1-O-(E)-4′-methoxybenzoyl-β-D-gluconic acid (2) were isolated from Lagotis yunnanensis, together with six previously known iridoid glucosides. The structures of these compounds were elucidated on the basis of spectral analysis, including 2D NMR spectroscopy. Published in Khimiya Prirodnykh Soedinenii, No. 6, pp. 529–530, November–December, 2006.