{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Park SH"],"funding":["NCATS NIH HHS","NICHD NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS","NIGMS NIH HHS","NIH HHS"],"pubmed_abstract":["Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome, and is estimated to affect one billion individuals worldwide. An increased intake of a high-fat diet (HFD) and sugar-sweetened beverages are risk-factors for NAFLD development, but how their combined intake promotes progression to a more severe form of liver injury is unknown. Here we show that fructose metabolism via ketohexokinase (KHK) C isoform increases endoplasmic reticulum (ER) stress in a dose dependent fashion, so when fructose is coupled with a HFD intake it leads to unresolved ER stress. Conversely, a liver-specific knockdown of KHK in C57BL/6J male mice consuming fructose on a HFD is adequate to improve the NAFLD activity score and exert a profound effect on the hepatic transcriptome. Over"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2023.01.27.525605"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9900898"],"repository":["biostudies-literature"],"pubmed_title":["Fructose Induced KHK-C Increases ER Stress and Modulates Hepatic Transcriptome to Drive Liver Disease in Diet-Induced and Genetic Models of NAFLD."],"pmcid":["PMC9900898"],"funding_grant_id":["K01 DK128022","R01 DK117850","P30 GM127211","K12 HD000850","R01 HL147883","UL1 TR001998","R01 DK067536","R01 DK099222","S10 OD028654"],"pubmed_authors":["Softic S","Helsley RN","Rose J","Fadhul T","Fujisaka S","Tu HC","Schilling B","Pan H","Divanovic S","Bons J","Pan C","Kahn CR","King CD","Kulkarni RN","Lusis AJ","Park SH","Willoughby JLS","Fitzgerald K","Gupta M","Noetzli L","Kern PA","Solheim MH","Dreyfuss JM"],"additional_accession":[]},"is_claimable":false,"name":"Fructose Induced KHK-C Increases ER Stress and Modulates Hepatic Transcriptome to Drive Liver Disease in Diet-Induced and Genetic Models of NAFLD.","description":"Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome, and is estimated to affect one billion individuals worldwide. An increased intake of a high-fat diet (HFD) and sugar-sweetened beverages are risk-factors for NAFLD development, but how their combined intake promotes progression to a more severe form of liver injury is unknown. Here we show that fructose metabolism via ketohexokinase (KHK) C isoform increases endoplasmic reticulum (ER) stress in a dose dependent fashion, so when fructose is coupled with a HFD intake it leads to unresolved ER stress. Conversely, a liver-specific knockdown of KHK in C57BL/6J male mice consuming fructose on a HFD is adequate to improve the NAFLD activity score and exert a profound effect on the hepatic transcriptome. Over","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2025-05-29T20:25:04.969Z","creation":"2025-05-29T20:25:04.969Z"},"accession":"S-EPMC9900898","cross_references":{"pubmed":["36747758"],"doi":["10.1101/2023.01.27.525605"]}}