SAT-673 The Effect of D-Allulose on Lipid Accumulation in HepG2 Hepatoblastoma Cells

Abstract Disclosure: M.J. Haas: None. K. Champagne: None. F. Warda: None. J. Batch-Joudi: None. L.D. Graham: None. N. Gupta: None. A.D. Mooradian: None. Lipid accumulation in hepatocytes in non-alcoholic steatohepatitis (NASH) is attributed partly to loss of insulin-responsiveness and/or an increased pro-inflammatory state. Since the rare sugar D-allulose has insulin mimetic and anti-inflammatory properties, its effects on lipid accumulation in liver-derived cells was tested. In HepG2 cells exposed to 200 μM oleic acid for 72 hours, D-allulose treatment decreased intracellular lipid accumulation with an IC50=0.45 ± 0.07 mM. A similar effect was observed in cells treated with 10 μM gemfibrozil. D-allulose and gemfibrozil treatment increased oleic acid β-oxidation. Both D-allulose and gemfibrozil increased peroxisome proliferator-activated receptor α (PPARα) expression (two-fold) relative to control cells, while retinoid X receptor was unchanged. D-allulose and gemfibrozil increased PPARα-dependent genes including those involved in fatty acid β-oxidation (acyl-coenzyme A oxidase 1, long-chain-fatty-acid-coenzyme A ligase 5, and carnitine palmitoyltransferase 1A). D-allulose and gemfibrozil also increased PPARα reporter gene expression and phosphorylation (Serine 12) which were both inhibited by the mitogen-activated protein (MAP) kinase inhibitor PD098059. Other MAP kinase inhibitors, including SB203580, SP600125, and BIX10289 had no effect on reporter gene expression. Oleic acid treatment, but not D-allulose or gemfibrozil, decreased sterol response element binding protein 1 and sterol response element binding protein 2 expression relative to cells not exposed to oleic acid, while peroxisome proliferator-activated receptor γ expression did not change. These results indicate that D-allulose mimics gemfibrozil effects on lipid content in HepG2 cells by promoting fatty acid β-oxidation via PPARα. Presentation: Saturday, July 12, 2025