Excess Fructose in High-Fructose Corn Syrup Reduces Cell Viability & Promotes Nitric Oxide Release in RAW 264.7 Macrophages

By Renzo Galarza, Edward Villegas

Faculty Mentor: Dr. Laura Sipe

Abstract

High-fructose corn syrup (HFCS) is an artificial sweetener that contains slightly higher concentrations of free fructose compared to standard sucrose. It has been linked to an increased risk of obesity, type 2 diabetes, cardiovascular disease, and fatty liver disease. While both HFCS and sucrose are widely used sweeteners, growing evidence suggests they may differ in their inflammatory potential. We sought to understand the effects of elevated fructose on RAW 264.7 macrophages. To investigate these effects, we treated the cells with either a sucrose solution or a solution designed to mimic high-fructose corn syrup. Lipopolysaccharide (LPS) stimulation was used to model innate immune activation. We assessed cell viability, nitric oxide (NO) release, IκB protein expression, and TNFα secretion. Compared to sucrose, higher fructose elicited a stronger pro-inflammatory response as indicated by increased NO release, as well as a greater cytotoxic effect. Interestingly, no significance was found in regards to IκB and TNFα expression. These findings indicate that higher fructose may play a more active role in promoting macrophage-mediated inflammation. Our research aims to understand how the composition of dietary sugars can differentially influence innate immune pathways and supports a mechanistic link between excessive fructose intake and the chronic inflammation underlying metabolic diseases.


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