Here, we showed that the development of NAFLD with early signs of inflammation in mice fed a high‐fructose, high‐fat and cholesterol‐rich diet even in the absence of overnutrition is associated with a loss of tight junction proteins and elevated levels of bacterial endotoxin in portal blood as well as an induction of the TLR4 signalling cascade in the liver. Here, TLR4 is linked to metabolic dysfunction-associated steatotic liver disease.