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.