, we speculate that it may be a potential dietary
factor that initiates inflammatory responses in the liver. Thus, the first
aim of the present study was to investigate whether a typical level of
dietary cholesterol (0.2% w/w) plays a role in the progression of hepatic
steatosis to NASH by inducing a second “hit”. Since insulin resistance,
oxidative stress [14], ER stress [15], inflammation [16] and mitochondrial
dysfunction [7] have been implicated in the pathogenesis of NAFLD, our
second aim was to investigate their possible role in the second “hit” in the
transition from hepatic steatosis toward NASH. Reported here are our
findings showing that, in the presence of hepatic steatosis, cholesterol
resulted in liver injury and inflammation within the liver. In addition,
cholesterol also persistently suppressed the expression of peroxisome
proliferator-activated receptor γ coactivator 1α (PGC1α) and mitochondrial
transcription factor A (TFAM) and mitochondrial fatty acid
oxidation. These findings provide novel insight into how a typical level
of dietary cholesterol may convert simple hepatic steatosis to NASH as a
trigger of the second “hit” in the pathogenesis of NAFLD.