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 beta-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.
Arakaki
Naokatu
N
Department of Molecular Cell Biology and Medicine, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan. arakaki@ph.tokushima-u.ac.jp
Kita
Toshiyuki
T
Shibata
Hirofumi
H
Higuti
Tomihiko
T
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000201:enzymology; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000906:Antibodies / Q000276:immunology; D016632:Apolipoprotein A-I / Q000378:metabolism; D002454:Cell Differentiation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D050356:Lipid Metabolism; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*
D017304:Annexin A5; D000906:Antibodies; D016632:Apolipoprotein A-I; D004791:Enzyme Inhibitors; D021122:Protein Subunits; D006180:Proton-Translocating ATPases