Fructose metabolism and its roles in metabolic diseases, inflammatory diseases, and cancer

Fructose, a prevalent hexose, has become a widely used food additive, with its usage rising significantly because of socio-economic advancements and shifts in human dietary habits. Excessive fructose intake has been implicated in obesity, cardiovascular disease, metabolic syndromes, inflammation, and cancer, among other disorders. This review discusses the absorption, distribution, and metabolism of fructose and the links between fructose metabolism and major metabolic pathways. The role of fructose in metabolic diseases, including metabolic dysfunction-associated fatty liver disease, hyperinsulinemia, and hyperuricemia, is also highlighted. Furthermore, the role of fructose in the development of chronic inflammation, including gut inflammation, liver inflammation, and neuroinflammation, is discussed. Lastly, in the context of cancer development, this review summarizes the dual role of fructose in tumors, both pro- and anti-tumor effects. Future studies on the role of fructose in cancer should focus on the complexity of physiological and pathological conditions, such as the specific tumor microenvironment and metabolic status. Fructose has been shown to induce metabolic reprogramming of multiple immune cells and increase pro-inflammatory immune responses; therefore, inhibiting or promoting its metabolism may regulate immune responses. And targeting fructose metabolism may be a promising approach to treating metabolic diseases, inflammation, and cancer.