Sweet death: Fructose as a metabolic toxin that targets the gut-liver axis

Glucose and fructose are closely related simple sugars, but fructose has been associated more closely with metabolic disease. Until the 1960s, the major dietary source of fructose was fruit, but subsequently, high-fructose corn syrup (HFCS) became a dominant component of the Western diet. The exponential increase in HFCS consumption correlates with the increased incidence of obesity and type 2 diabetes mellitus, but the mechanistic link between these metabolic diseases and fructose remains tenuous. Although dietary fructose was thought to be metabolized exclusively in the liver, evidence has emerged that it is also metabolized in the small intestine and leads to intestinal epithelial barrier deterioration. Along with the clinical manifestations of hereditary fructose intolerance, these findings suggest that, along with the direct effect of fructose on liver metabolism, the gut-liver axis plays a key role in fructose metabolism and pathology. Here, we summarize recent studies on fructose biology and pathology and discuss new opportunities for prevention and treatment of diseases associated with high-fructose consumption.

Automated summary

Fructose is closely related to metabolic diseases, with consumption of high-fructose corn syrup correlating with increased rates of obesity and diabetes. In addition to being metabolized in the liver, fructose has been found to be metabolized in the small intestine, leading to deterioration of the intestinal epithelial barrier. The gut-liver axis plays a key role in fructose metabolism and pathology, along with the direct effects of fructose on liver metabolism.