石橋 賢一

The amount of intake of elaidate, an industrially produced trans fatty acid, is associated with the development of cardiovascular disease. Recently, we revealed that persistent exposure to elaidate is also involved in an impairment of insulin responsiveness of adipocytes. Moreover, in the process of investigation, we revealed that extracellular elaidate is incorporated into phospholipid and triglyceride, and mainly exist as triglyceride in adipocytes. Since fatty acids in adipocytes are not only used as energy source but also released for regulation of cellular function and whole-body metabolism as cytokines, we hypothesized that incorporated elaidate into adipocytes is released and affects around cells. Here, we examined how intracellular elaidate is mainly exist as triglyceride and whether elaidate is released from adipocytes. Elaidate tended to be incorporated into triglyceride compared with phospholipid, and incorporated elaidate in triglyceride was not decreased in observed periods. Under lipolytic stimulation, incorporated elaidate is released from adipocytes along with other fatty acids. These results suggest that adipocytes act as a reservoir and supplier of elaidate, and may affect around of adipocytes.

Dietary intake of elaidate (elaidic acid), a trans fatty acid, is associated with the development of various diseases. Because elaidate is a C18 unsaturated fatty acid with a steric structure similar to that of a C18 saturated fatty acid (stearate), we previously revealed that insulin-dependent glucose uptake was impaired in adipocytes exposed to elaidate before and during differentiation similar to stearate. However, it has remained unknown whether the mechanism of impairment of insulin-dependent glucose uptake due to elaidate is similar to that of stearate. Here, we show that persistent exposure to elaidate has particular effects on insulin signaling and GLUT4 dynamics. Insulin-induced accumulation of Akt at the plasma membrane and elevations of phosphorylated Akt and AS160 levels in whole cells were suppressed in adipocytes after persistent exposure to 50 µM elaidate. Intriguingly, persistent exposure to the same concentration of stearate did not affect the levels of phosphorylated Akt and AS160. When cells were exposed to these fatty acids, elaidate suppressed insulin-induced fusion, but not translocation, of GLUT4 storage vesicles with the plasma membrane. Conversely, stearate did not suppress the fusion and translocation of GLUT4 storage. These results suggest that elaidate exhibits suppressive effects on the accumulation of Akt and fusion of GLUT4 storage vesicles, and that elaidate and stearate differ in the mechanisms by which they impair insulin-dependent glucose uptake.