Combatting the Fructose Epidemic: Fruitful or Fruitless?

Non-alcoholic fatty liver disease (NAFLD) and its cardiometabolic consequences are a major health burden worldwide. Intrahepatic lipid (IHL) accumulation is the first stage of NAFLD. IHL content is, among others, driven by the conversion of simple sugars into fatty acids via hepatic de novo lipogenesis (DNL). However, which simple sugar – fructose or glucose – plays a greater role in the augmentation of DNL has been the subject of much debate.Therefore, this thesis investigated the role of fructose in the pathophysiology of NAFLD, and the possible underlying mechanism. First, experiments in mice and healthy individuals did not elucidate the key molecular mechanisms by which fructose participates as a signaling molecule in the pathogenesis of IHL accumulation. Second, nutritional and epidemiological studies collectively show that fructose plays a presumptive causal role in the pathogenesis of IHL accumulation, type 2 diabetes, hypertension, myocardial infarction, and colorectal cancer. In particular, fructose from fruit juice and sugar-sweetened beverages, but not from fruit, is associated with a higher IHL content.