Cell-autonomous adiposity through increased cell surface GLUT4 due to ankyrin-B deficiency.
Obesity typically is linked to caloric imbalance as a result of overnutrition. Here we propose a cell-autonomous mechanism for adiposity as a result of persistent cell surface glucose transporter type 4 (GLUT4) in adipocytes resulting from impaired function of ankyrin-B (AnkB) in coupling GLUT4 to clathrin-mediated endocytosis. Adipose tissue-specific AnkB-KO mice develop obesity and progressive pancreatic islet dysfunction with age or high-fat diet (HFD). AnkB-deficient adipocytes exhibit increased lipid accumulation associated with increased glucose uptake and impaired endocytosis of GLUT4. AnkB binds directly to GLUT4 and clathrin and promotes their association in adipocytes. AnkB variants that fail to restore normal lipid accumulation and GLUT4 localization in adipocytes are present in 1.3% of European Americans and 8.4% of African Americans, and are candidates to contribute to obesity susceptibility in humans.
['Lorenzo|Damaris N|DN|0000-0002-6856-2988', 'Bennett|Vann|V|']
D017667:Adipocytes D050154:Adiposity D000818:Animals D017487:Ankyrins D001692:Biological Transport D044383:Blacks D002966:Clathrin D059305:Diet, High-Fat D004705:Endocytosis D005786:Gene Expression Regulation D005947:Glucose D051275:Glucose Transporter Type 4 D006801:Humans D007515:Islets of Langerhans D008297:Male D051379:Mice D018345:Mice, Knockout D008958:Models, Molecular D009154:Mutation D009765:Obesity D011485:Protein Binding D017433:Protein Structure, Secondary D015398:Signal Transduction D044465:Whites
Glut4 ankyrin-B obesity clathrin membrane transport