Figure 2.

Excessive fructose intake is associated with inflammation, cellular stress, dysbiosis, and hepatic steatosis. Fructose strongly activates DNL, inducing IR and liver inflammation. Fructose metabolism by fructokinase (KHK–C) leads to uric acid generation, mitochondrial dysfunction, and oxidative stress, which contributes to hepatic IR and inflammation. Additionally, high fructose consumption induces gut microbiota dysbiosis, which increases gut permeability, leading to translocation of bacterial endotoxins, cytokines, and lipopolysaccharide (LPS), thus driving hepatic inflammation and IR. Finally, fructose increases peripheral IR through LPS, cytokines, and lipid oxidation and negatively influences appetite through gut–brain axis alterations, high palatability, and leptin modulation, thereby promoting increased energy intake and weight gain [95,96,97,98,99]. Upwards pointing arrows (↑) indicate increase, downwards pointing arrows (↓) indicate decrease.