Stress can attenuate hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in mice with nonalcoholic steatohepatitis

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 aci...

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Veröffentlicht in:Laboratory investigation 2021-02, Vol.101 (2), p.193-203
Hauptverfasser: Takada, Sayuri, Matsubara, Tsutomu, Fujii, Hideki, Sato-Matsubara, Misako, Daikoku, Atsuko, Odagiri, Naoshi, Amano-Teranishi, Yuga, Kawada, Norifumi, Ikeda, Kazuo
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container_issue 2
container_start_page 193
container_title Laboratory investigation
container_volume 101
creator Takada, Sayuri
Matsubara, Tsutomu
Fujii, Hideki
Sato-Matsubara, Misako
Daikoku, Atsuko
Odagiri, Naoshi
Amano-Teranishi, Yuga
Kawada, Norifumi
Ikeda, Kazuo
description 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. Chronic stress can change hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in nonalcoholic steatohepatitis mice, disrupting bile acid homeostasis by induction of hepatic Cyp7a1 expression. This study describes a new role βMCA in the liver, indicating its potential usefulness for nonalcohol fatty liver disease therapy.
doi_str_mv 10.1038/s41374-020-00509-x
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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. 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ispartof Laboratory investigation, 2021-02, Vol.101 (2), p.193-203
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language eng
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subjects 101/58
38/1
38/77
631/443/319/1557
631/443/319/2723
64/60
82/80
Accumulation
Acids
Animals
Bile
Cells, Cultured
Cholesterol 7-alpha-Hydroxylase - metabolism
Cholic acid
Cholic Acids - analysis
Cholic Acids - metabolism
Choline
Corticosterone
Cortisol
Disruption
Fatty liver
Hepatocytes
Hepatocytes - metabolism
Homeostasis
Laboratory Medicine
Lipid Metabolism - physiology
Lipids
Liver
Liver - chemistry
Liver - metabolism
Liver - physiology
Liver diseases
Male
Medicine
Medicine & Public Health
Methionine
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease - metabolism
Nutrient deficiency
Oleic acid
Palmitic acid
Pathology
Proteins
Stress
Stress, Psychological - metabolism
title Stress can attenuate hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in mice with nonalcoholic steatohepatitis
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