Stress can affect our body and is known to lead to some diseases. However, the influence on the development of nonalcohol
fatty liver disease (
NAFLD) remains unknown. This study demonstrated that chronic restraint stress attenuated hepatic
lipid accumulation via elevation of hepatic β-
muricholic acid (βMCA) levels in the development of
nonalcoholic steatohepatitis (NASH) in mice. Serum
cortisol and
corticosterone levels, i.e., human and rodent stress markers, were correlated with serum
bile acid levels in patients with
NAFLD and
methionine- and
choline-deficient (MCD) diet-induced mice, respectively, suggesting that stress is related to
bile acid (BA) homeostasis in NASH. In the mouse model, hepatic βMCA and
cholic acid (CA) levels were increased after the stress challenge. Considering that a short stress enhanced hepatic CYP7A1
protein levels in normal mice and
corticosterone increased CYP7A1
protein levels in primary mouse hepatocytes, the enhanced Cyp7a1 expression was postulated to be involved in the chronic stress-increased hepatic βMCA level. Interestingly, chronic stress decreased hepatic
lipid levels in MCD-induced NASH mice. Furthermore, βMCA suppressed
lipid accumulation in mouse primary hepatocytes exposed to
palmitic acid/
oleic acid, but CA did not. In addition, Cyp7a1 expression seemed to be related to
lipid accumulation in hepatocytes. In conclusion, chronic stress can change hepatic
lipid accumulation in NASH mice, disrupting BA homeostasis via induction of hepatic Cyp7a1 expression. This study discovered a new βMCA action in the liver, indicating the possibility that βMCA is available for
NAFLD therapy.