Excessive accumulation of
triglycerides (TG) in liver, in the absence of significant alcohol consumption is
nonalcoholic fatty liver disease (
NAFLD).
NAFLD is a significant risk factor for developing
cirrhosis and an independent predictor of
cardiovascular disease.
High fructose corn syrup (HFCS)-containing beverages were associated with metabolic abnormalities, and contributed to the development of
NAFLD in human trials. Ingested
carbohydrates are a major stimulus for hepatic de novo lipogenesis (DNL) and are more likely to directly contribute to
NAFLD than
dietary fat. Substrates used for the synthesis of newly made
fatty acids by DNL are primarily
glucose,
fructose, and
amino acids. Epidemiological studies linked HFCS consumption to the severity of
fibrosis in patients with
NAFLD. New animal studies provided additional evidence on the role of
carbohydrate-induced DNL and the gut microbiome in
NAFLD. The excessive consumption of HFCS-55 increased endoplasmic reticulum stress, activated the stress-related
kinase, caused
mitochondrial dysfunction, and increased apoptotic activity in the liver. A link between dietary
fructose intake, increased hepatic
glucose transporter type-5 (Glut5) (
fructose transporter) gene expression and hepatic lipid peroxidation, MyD88, TNF-α levels, gut-derived
endotoxemia, toll-like receptor-4, and
NAFLD was reported. The lipogenic and proinflammatory effects of
fructose appear to be due to transient
ATP depletion by its rapid phosphorylation within the cell and from its ability to raise intracellular and serum
uric acid levels. However, large prospective studies that evaluated the relationship between
fructose and
NAFLD were not performed yet.