The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe
Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether...
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| Veröffentlicht in: | The Journal of nutritional biochemistry 2016-09, Vol.35, p.66-73 |
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| creator | Shimabukuro, Michio Okawa, Chinami Yamada, Hirotsugu Yanagi, Shuhei Uematsu, Etsuko Sugasawa, Noriko Kurobe, Hirotsugu Hirata, Yoichiro Kim-Kaneyama, Joo-ri Lei, Xiao-Feng Takao, Shoichiro Tanaka, Yasutake Fukuda, Daiju Yagi, Shusuke Soeki, Takeshi Kitagawa, Tetsuya Masuzaki, Hiroaki Sato, Masao Sata, Masataka |
| description | Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD+Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD+E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function. |
| doi_str_mv | 10.1016/j.jnutbio.2016.05.010 |
| format | Article |
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To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD+Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD+E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function.</description><identifier>ISSN: 0955-2863</identifier><identifier>EISSN: 1873-4847</identifier><identifier>DOI: 10.1016/j.jnutbio.2016.05.010</identifier><identifier>PMID: 27416363</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adipose Tissue, White - drug effects ; Adipose Tissue, White - pathology ; Adiposity - drug effects ; Animals ; Anticholesteremic Agents - therapeutic use ; Cardiac function ; Cardiac hypertrophy ; Cardiomegaly - etiology ; Cardiomegaly - prevention & control ; Cholesterol - adverse effects ; Cholesterol - analogs & derivatives ; Cholesterol - blood ; Cholesterol - metabolism ; Epicardial fat ; Ezetimibe - therapeutic use ; Gastrointestinal Agents - therapeutic use ; Gene Expression Regulation, Enzymologic - drug effects ; Heart - drug effects ; Heart - physiopathology ; Heart Diseases - etiology ; Heart Diseases - metabolism ; Heart Diseases - pathology ; Heart Diseases - physiopathology ; Hydroxycholesterols - antagonists & inhibitors ; Hydroxycholesterols - blood ; Hydroxycholesterols - metabolism ; Hyperphagia - physiopathology ; Intestinal Absorption - drug effects ; Lipoproteins, LDL - adverse effects ; Lipoproteins, LDL - blood ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Male ; Myocardium - enzymology ; Myocardium - metabolism ; Myocardium - pathology ; Obesity ; Oxidation-Reduction ; Oxycholesterol ; Pericardium ; Random Allocation ; Sus scrofa</subject><ispartof>The Journal of nutritional biochemistry, 2016-09, Vol.35, p.66-73</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-aa64d5f53902b9fda827e584674331017927b9bd9e7815e0fe2774a5ca3eb85b3</citedby><cites>FETCH-LOGICAL-c365t-aa64d5f53902b9fda827e584674331017927b9bd9e7815e0fe2774a5ca3eb85b3</cites><orcidid>0000-0001-7835-7665</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jnutbio.2016.05.010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27416363$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimabukuro, Michio</creatorcontrib><creatorcontrib>Okawa, Chinami</creatorcontrib><creatorcontrib>Yamada, Hirotsugu</creatorcontrib><creatorcontrib>Yanagi, Shuhei</creatorcontrib><creatorcontrib>Uematsu, Etsuko</creatorcontrib><creatorcontrib>Sugasawa, Noriko</creatorcontrib><creatorcontrib>Kurobe, Hirotsugu</creatorcontrib><creatorcontrib>Hirata, Yoichiro</creatorcontrib><creatorcontrib>Kim-Kaneyama, Joo-ri</creatorcontrib><creatorcontrib>Lei, Xiao-Feng</creatorcontrib><creatorcontrib>Takao, Shoichiro</creatorcontrib><creatorcontrib>Tanaka, Yasutake</creatorcontrib><creatorcontrib>Fukuda, Daiju</creatorcontrib><creatorcontrib>Yagi, Shusuke</creatorcontrib><creatorcontrib>Soeki, Takeshi</creatorcontrib><creatorcontrib>Kitagawa, Tetsuya</creatorcontrib><creatorcontrib>Masuzaki, Hiroaki</creatorcontrib><creatorcontrib>Sato, Masao</creatorcontrib><creatorcontrib>Sata, Masataka</creatorcontrib><title>The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe</title><title>The Journal of nutritional biochemistry</title><addtitle>J Nutr Biochem</addtitle><description>Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD+Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD+E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function.</description><subject>Adipose Tissue, White - drug effects</subject><subject>Adipose Tissue, White - pathology</subject><subject>Adiposity - drug effects</subject><subject>Animals</subject><subject>Anticholesteremic Agents - therapeutic use</subject><subject>Cardiac function</subject><subject>Cardiac hypertrophy</subject><subject>Cardiomegaly - etiology</subject><subject>Cardiomegaly - prevention & control</subject><subject>Cholesterol - adverse effects</subject><subject>Cholesterol - analogs & derivatives</subject><subject>Cholesterol - blood</subject><subject>Cholesterol - metabolism</subject><subject>Epicardial fat</subject><subject>Ezetimibe - therapeutic use</subject><subject>Gastrointestinal Agents - therapeutic use</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Heart - drug effects</subject><subject>Heart - physiopathology</subject><subject>Heart Diseases - etiology</subject><subject>Heart Diseases - metabolism</subject><subject>Heart Diseases - pathology</subject><subject>Heart Diseases - physiopathology</subject><subject>Hydroxycholesterols - antagonists & inhibitors</subject><subject>Hydroxycholesterols - blood</subject><subject>Hydroxycholesterols - metabolism</subject><subject>Hyperphagia - physiopathology</subject><subject>Intestinal Absorption - drug effects</subject><subject>Lipoproteins, LDL - adverse effects</subject><subject>Lipoproteins, LDL - blood</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>Myocardium - enzymology</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Obesity</subject><subject>Oxidation-Reduction</subject><subject>Oxycholesterol</subject><subject>Pericardium</subject><subject>Random Allocation</subject><subject>Sus scrofa</subject><issn>0955-2863</issn><issn>1873-4847</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuO1DAQRSMEYpqBTwB5yYIEO4njhA1CI17SSGyGteVHZVKttB1sh6HnR_kdHLpB7FhZrjq3btm3KJ4zWjHKutf7au_WpNFXdb5WlFeU0QfFjvWiKdu-FQ-LHR04L-u-ay6KJzHuKaV1y7vHxUUtWtY1XbMrft5MQBaVJr9Mx4h-9rdo1EyCn4H4kfgfaPEeLDFTrsQEuREJOgJL5oLFzI4qEWXMelhnldA7olzmfzcNscc4rs5s9TdEkZhWe9z08Q4dkDFPVmTC2ykLZh8wCxASucM05TEZnFBj8mHbBV3KG6DLlv9sQ5SOPiybwSsC95DwgBqeFo9GNUd4dj4vi68f3t9cfSqvv3z8fPXuujRNx1OpVNdaPvJmoLUeRqv6WgDv2060TZP_WQy10IO2A4iecaAj1EK0ihvVgO65bi6Ll6e5S_Df1rySPGA0MM_KgV-jZD1ru76uRZ9RfkJN8DEGGOUS8KDCUTIqt0zlXp4zlVumknKZM826F2eLVR_A_lX9CTEDb08A5Id-RwgyGgRnwGIAk6T1-B-LXwXYu8s</recordid><startdate>201609</startdate><enddate>201609</enddate><creator>Shimabukuro, Michio</creator><creator>Okawa, Chinami</creator><creator>Yamada, Hirotsugu</creator><creator>Yanagi, Shuhei</creator><creator>Uematsu, Etsuko</creator><creator>Sugasawa, Noriko</creator><creator>Kurobe, Hirotsugu</creator><creator>Hirata, Yoichiro</creator><creator>Kim-Kaneyama, Joo-ri</creator><creator>Lei, Xiao-Feng</creator><creator>Takao, Shoichiro</creator><creator>Tanaka, Yasutake</creator><creator>Fukuda, Daiju</creator><creator>Yagi, Shusuke</creator><creator>Soeki, Takeshi</creator><creator>Kitagawa, Tetsuya</creator><creator>Masuzaki, Hiroaki</creator><creator>Sato, Masao</creator><creator>Sata, Masataka</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7835-7665</orcidid></search><sort><creationdate>201609</creationdate><title>The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe</title><author>Shimabukuro, Michio ; Okawa, Chinami ; Yamada, Hirotsugu ; Yanagi, Shuhei ; Uematsu, Etsuko ; Sugasawa, Noriko ; Kurobe, Hirotsugu ; Hirata, Yoichiro ; Kim-Kaneyama, Joo-ri ; Lei, Xiao-Feng ; Takao, Shoichiro ; Tanaka, Yasutake ; Fukuda, Daiju ; Yagi, Shusuke ; Soeki, Takeshi ; Kitagawa, Tetsuya ; Masuzaki, Hiroaki ; Sato, Masao ; Sata, Masataka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-aa64d5f53902b9fda827e584674331017927b9bd9e7815e0fe2774a5ca3eb85b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adipose Tissue, White - drug effects</topic><topic>Adipose Tissue, White - pathology</topic><topic>Adiposity - drug effects</topic><topic>Animals</topic><topic>Anticholesteremic Agents - therapeutic use</topic><topic>Cardiac function</topic><topic>Cardiac hypertrophy</topic><topic>Cardiomegaly - etiology</topic><topic>Cardiomegaly - prevention & control</topic><topic>Cholesterol - adverse effects</topic><topic>Cholesterol - analogs & derivatives</topic><topic>Cholesterol - blood</topic><topic>Cholesterol - metabolism</topic><topic>Epicardial fat</topic><topic>Ezetimibe - therapeutic use</topic><topic>Gastrointestinal Agents - therapeutic use</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Heart - drug effects</topic><topic>Heart - physiopathology</topic><topic>Heart Diseases - etiology</topic><topic>Heart Diseases - metabolism</topic><topic>Heart Diseases - pathology</topic><topic>Heart Diseases - physiopathology</topic><topic>Hydroxycholesterols - antagonists & inhibitors</topic><topic>Hydroxycholesterols - blood</topic><topic>Hydroxycholesterols - metabolism</topic><topic>Hyperphagia - physiopathology</topic><topic>Intestinal Absorption - drug effects</topic><topic>Lipoproteins, LDL - adverse effects</topic><topic>Lipoproteins, LDL - blood</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>Myocardium - enzymology</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Obesity</topic><topic>Oxidation-Reduction</topic><topic>Oxycholesterol</topic><topic>Pericardium</topic><topic>Random Allocation</topic><topic>Sus scrofa</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shimabukuro, Michio</creatorcontrib><creatorcontrib>Okawa, Chinami</creatorcontrib><creatorcontrib>Yamada, Hirotsugu</creatorcontrib><creatorcontrib>Yanagi, Shuhei</creatorcontrib><creatorcontrib>Uematsu, Etsuko</creatorcontrib><creatorcontrib>Sugasawa, Noriko</creatorcontrib><creatorcontrib>Kurobe, Hirotsugu</creatorcontrib><creatorcontrib>Hirata, Yoichiro</creatorcontrib><creatorcontrib>Kim-Kaneyama, Joo-ri</creatorcontrib><creatorcontrib>Lei, Xiao-Feng</creatorcontrib><creatorcontrib>Takao, Shoichiro</creatorcontrib><creatorcontrib>Tanaka, Yasutake</creatorcontrib><creatorcontrib>Fukuda, Daiju</creatorcontrib><creatorcontrib>Yagi, Shusuke</creatorcontrib><creatorcontrib>Soeki, Takeshi</creatorcontrib><creatorcontrib>Kitagawa, Tetsuya</creatorcontrib><creatorcontrib>Masuzaki, Hiroaki</creatorcontrib><creatorcontrib>Sato, Masao</creatorcontrib><creatorcontrib>Sata, Masataka</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of nutritional biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shimabukuro, Michio</au><au>Okawa, Chinami</au><au>Yamada, Hirotsugu</au><au>Yanagi, Shuhei</au><au>Uematsu, Etsuko</au><au>Sugasawa, Noriko</au><au>Kurobe, Hirotsugu</au><au>Hirata, Yoichiro</au><au>Kim-Kaneyama, Joo-ri</au><au>Lei, Xiao-Feng</au><au>Takao, Shoichiro</au><au>Tanaka, Yasutake</au><au>Fukuda, Daiju</au><au>Yagi, Shusuke</au><au>Soeki, Takeshi</au><au>Kitagawa, Tetsuya</au><au>Masuzaki, Hiroaki</au><au>Sato, Masao</au><au>Sata, Masataka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe</atitle><jtitle>The Journal of nutritional biochemistry</jtitle><addtitle>J Nutr Biochem</addtitle><date>2016-09</date><risdate>2016</risdate><volume>35</volume><spage>66</spage><epage>73</epage><pages>66-73</pages><issn>0955-2863</issn><eissn>1873-4847</eissn><abstract>Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD+Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD+E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27416363</pmid><doi>10.1016/j.jnutbio.2016.05.010</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-7835-7665</orcidid></addata></record> |
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| subjects | Adipose Tissue, White - drug effects Adipose Tissue, White - pathology Adiposity - drug effects Animals Anticholesteremic Agents - therapeutic use Cardiac function Cardiac hypertrophy Cardiomegaly - etiology Cardiomegaly - prevention & control Cholesterol - adverse effects Cholesterol - analogs & derivatives Cholesterol - blood Cholesterol - metabolism Epicardial fat Ezetimibe - therapeutic use Gastrointestinal Agents - therapeutic use Gene Expression Regulation, Enzymologic - drug effects Heart - drug effects Heart - physiopathology Heart Diseases - etiology Heart Diseases - metabolism Heart Diseases - pathology Heart Diseases - physiopathology Hydroxycholesterols - antagonists & inhibitors Hydroxycholesterols - blood Hydroxycholesterols - metabolism Hyperphagia - physiopathology Intestinal Absorption - drug effects Lipoproteins, LDL - adverse effects Lipoproteins, LDL - blood Liver - drug effects Liver - metabolism Liver - pathology Male Myocardium - enzymology Myocardium - metabolism Myocardium - pathology Obesity Oxidation-Reduction Oxycholesterol Pericardium Random Allocation Sus scrofa |
| title | The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe |
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