Research paper
Softic S, Gupta MK, Wang GX, Fujisaka S, O'Neill BT, Rao TN, Willoughby J, Harbison C, Fitzgerald K, Ilkayeva O, Newgard CB, Cohen DE, Kahn CR. Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling. Journal of Clinical Investigation. 2017 Nov 1;127(11):4059-4074. DOI: 10.1172/JCI94585. PMID: 28972537. PMCID: PMC5663363.
Why we cite it
Provides the mechanistic explanation for why fructose is uniquely harmful to the liver compared to glucose: despite identical caloric intake, fructose activates a distinct transcriptional pathway (SREBP1c) that drives de novo fatty acid synthesis and insulin resistance, while glucose activates a different pathway (ChREBP) associated with preserved insulin signaling. Critical context dependency — these divergent effects only emerge on a high-fat diet, suggesting fructose is particularly dangerous in the context of a Western diet. Also provides human data linking ketohexokinase elevation to NASH progression.