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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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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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.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/s41374-020-00509-x</identifier><identifier>PMID: 33303970</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>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</subject><ispartof>Laboratory investigation, 2021-02, Vol.101 (2), p.193-203</ispartof><rights>2020 United States & Canadian Academy of Pathology</rights><rights>The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2020</rights><rights>The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c516t-94495bc175ac864d33a33842ff0b6a2bc9adb30cc345e4a9a8a3fe3da2e856e23</citedby><cites>FETCH-LOGICAL-c516t-94495bc175ac864d33a33842ff0b6a2bc9adb30cc345e4a9a8a3fe3da2e856e23</cites><orcidid>0000-0003-1100-1052</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33303970$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takada, Sayuri</creatorcontrib><creatorcontrib>Matsubara, Tsutomu</creatorcontrib><creatorcontrib>Fujii, Hideki</creatorcontrib><creatorcontrib>Sato-Matsubara, Misako</creatorcontrib><creatorcontrib>Daikoku, Atsuko</creatorcontrib><creatorcontrib>Odagiri, Naoshi</creatorcontrib><creatorcontrib>Amano-Teranishi, Yuga</creatorcontrib><creatorcontrib>Kawada, Norifumi</creatorcontrib><creatorcontrib>Ikeda, Kazuo</creatorcontrib><title>Stress can attenuate hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in mice with nonalcoholic steatohepatitis</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><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.</description><subject>101/58</subject><subject>38/1</subject><subject>38/77</subject><subject>631/443/319/1557</subject><subject>631/443/319/2723</subject><subject>64/60</subject><subject>82/80</subject><subject>Accumulation</subject><subject>Acids</subject><subject>Animals</subject><subject>Bile</subject><subject>Cells, Cultured</subject><subject>Cholesterol 7-alpha-Hydroxylase - metabolism</subject><subject>Cholic acid</subject><subject>Cholic Acids - analysis</subject><subject>Cholic Acids - metabolism</subject><subject>Choline</subject><subject>Corticosterone</subject><subject>Cortisol</subject><subject>Disruption</subject><subject>Fatty liver</subject><subject>Hepatocytes</subject><subject>Hepatocytes - metabolism</subject><subject>Homeostasis</subject><subject>Laboratory Medicine</subject><subject>Lipid Metabolism - physiology</subject><subject>Lipids</subject><subject>Liver</subject><subject>Liver - 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Academic</collection><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takada, Sayuri</au><au>Matsubara, Tsutomu</au><au>Fujii, Hideki</au><au>Sato-Matsubara, Misako</au><au>Daikoku, Atsuko</au><au>Odagiri, Naoshi</au><au>Amano-Teranishi, Yuga</au><au>Kawada, Norifumi</au><au>Ikeda, Kazuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stress can attenuate hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in mice with nonalcoholic steatohepatitis</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><addtitle>Lab Invest</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>101</volume><issue>2</issue><spage>193</spage><epage>203</epage><pages>193-203</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><abstract>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.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>33303970</pmid><doi>10.1038/s41374-020-00509-x</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1100-1052</orcidid><oa>free_for_read</oa></addata></record> |
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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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