Cell-surface H+-ATP synthase as a potential molecular target for anti-obesity drugs

Here we show that the cell-surface expression of the alpha subunit of H+-ATP synthase is markedly increased during adipocyte differentiation. Treatment of differentiated adipocytes with small molecule inhibitors of H+-ATP synthase or antibodies against alpha and beta subunits of H+-ATP synthase leads to a decrease in cytosolic lipid droplet accumulation. Apolipoprotein A-I, which has been shown to bind to the ectopic β-chain of H+-ATP synthase and inhibit the activity of cell-surface H+-ATP synthase, also was found to inhibit cytosolic lipid accumulation. These results suggest that the cell-surface H+-ATP synthase has a previously unsuspected role in lipid metabolism in adipocytes.