SAT-LB057 High-Fructose Corn Syrup Enhances Intestinal Tumor Growth in Mice

Abstract

An increasing number of studies have suggested a potential link between sugar consumption and cancer. However, a direct relationship between the two remains controversial. Here, we treated APC-mutant mice daily with a modest amount of high-fructose corn syrup (HFCS) via oral gavage to mimic sugar-sweetened beverage (SSB) consumption and evaluated the effects of SSBs on intestinal tumorigenesis. We observed a dramatic increase in tumor size and tumor grade in HFCS-treated mice despite no signs of obesity or metabolic syndrome. A bolus of HFCS spikes the level of fructose and glucose in the intestinal lumen and serum, respectively, allowing tumors to take up both sugars efficiently. Ketohexokinase (KHK) in tumors rapidly converts fructose to fructose-1-phosphate (F1P), lowering cytosolic ATP in the process. Consequently, this leads to the activation of glycolysis as ATP depletion relieves the allosteric inhibition of phosphofructokinase (PFK), the most critical regulatory enzyme in glycolysis. This accelerated glycolysis contributes to the increased de novo lipogenesis pathway that enhances tumor growth in HFCS-treated mice. Importantly, the deletion of KHK or fatty acid synthase (FASN) in APC-mutant mice abolishes the HFCS-induced metabolic changes and tumor growth. Overall, our results provide a mechanistic rationale for restricting SSB consumption to decrease the rate of growth of early stage colorectal cancers. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.