Nonalcoholic fatty liver disease (
NAFLD) is the most common chronic
liver disease in the world. Disturbed
cholesterol metabolism plays a crucial role in the development of
NAFLD. The present study was conducted to evaluate the effects of EPA-PC extracted from sea cucumber on
liver steatosis and
cholesterol metabolism in
NAFLD. Male Wistar rats were randomly divided into seven groups (normal control group, model group,
lovastatin group, low- and high-dose EPA groups, and low- and high-dose EPA-PC groups). Model rats were established by administering a diet containing 1%
orotic acid. To determine the possible
cholesterol metabolism promoting mechanism of EPA-PC, we analyzed the transcription of key genes and transcriptional factors involved in hepatic
cholesterol metabolism. EPA-PC dramatically alleviated hepatic
lipid accumulation, reduced the serum TC concentration, and elevated HDLC levels in
NAFLD rats. Fecal neutral
cholesterol excretion was also promoted by EPA-PC administration. Additionally, EPA-PC decreased the
mRNA expression of hydroxymethyl
glutaric acid acyl (HMGR) and
cholesterol 7α-hydroxylase (
CYP7A), and increased the transcription of
sterol carrying
protein 2 (SCP2). Moreover, EPA-PC stimulated the transcription of
peroxisome proliferators-activated receptor α (PPARα) and
adenosine monophosphate activated
protein kinase (AMPK) as well as its modulators, liver
kinase B1 (LKB1) and Ca2+/
calmodulin-dependent
kinase kinase (
CAMKK). Based on the results, the promoting effects of EPA-PC on
NAFLD may be partly associated with the suppression of
cholesterol synthesis via HMGR inhibition and the enhancement of fecal
cholesterol excretion through increased SCP2 transcription. The underlying mechanism may involve stimulation of PPARα and AMPK.