18β‐glycyrrhetinic acid attenuates anandamide‐induced adiposity and high‐fat diet induced obesity
SCOPE: Previous reports suggest that licorice extract has various metabolically beneficial effects and may help to alleviate adiposity and hyperlipidemia. However, underlying anti‐obesity mechanisms still remain elusive. Moreover, it is unknown which single ingredient in licorice extract would media...
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| Veröffentlicht in: | Molecular nutrition & food research 2014-07, Vol.58 (7), p.1436-1446 |
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| creator | Park, Miyoung Lee, Ji‐Hae Choi, Jin Kyu Hong, Yong Deog Bae, Il‐Hong Lim, Kyung‐Min Park, Young‐Ho Ha, Hunjoo |
| description | SCOPE: Previous reports suggest that licorice extract has various metabolically beneficial effects and may help to alleviate adiposity and hyperlipidemia. However, underlying anti‐obesity mechanisms still remain elusive. Moreover, it is unknown which single ingredient in licorice extract would mediate such effects. We aimed to demonstrate that licorice extract and its active ingredients can inhibit adipocyte differentiation and fat accumulation. METHODS AND RESULTS: 18β‐glycyrrhetinic acid (18β‐GA) alleviated the effects of CB1R agonist, anandamide (AEA) on CB1R signaling in a concentration‐dependent manner. Consistently, 18β‐GA suppressed AEA‐induced adipocyte differentiation in 3T3‐L1 cells through the downregulation of AEA‐induced MAPK activation and expression of adipogenic genes including C/EBP‐α and PPAR‐γ. The protein levels of fatty acid synthase and stearoyl‐CoA desaturase 1 were also decreased and the phosphorylation of acetyl‐CoA carboxylase was increased in 18β‐GA pretreated cells. The supplementation of 18β‐GA significantly lowered body weight, fat weight, and plasma lipids levels in obese animal models. CONCLUSION: These results may provide a novel insight into the molecular mechanism involved in anti‐adipogenic and anti‐obesity effects of 18β‐GA by suppressing the activation of CB1R induced by AEA. Thus, 18β‐GA may exert beneficial effects against obesity‐related metabolic disorders. |
| doi_str_mv | 10.1002/mnfr.201300763 |
| format | Article |
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However, underlying anti‐obesity mechanisms still remain elusive. Moreover, it is unknown which single ingredient in licorice extract would mediate such effects. We aimed to demonstrate that licorice extract and its active ingredients can inhibit adipocyte differentiation and fat accumulation. METHODS AND RESULTS: 18β‐glycyrrhetinic acid (18β‐GA) alleviated the effects of CB1R agonist, anandamide (AEA) on CB1R signaling in a concentration‐dependent manner. Consistently, 18β‐GA suppressed AEA‐induced adipocyte differentiation in 3T3‐L1 cells through the downregulation of AEA‐induced MAPK activation and expression of adipogenic genes including C/EBP‐α and PPAR‐γ. The protein levels of fatty acid synthase and stearoyl‐CoA desaturase 1 were also decreased and the phosphorylation of acetyl‐CoA carboxylase was increased in 18β‐GA pretreated cells. The supplementation of 18β‐GA significantly lowered body weight, fat weight, and plasma lipids levels in obese animal models. CONCLUSION: These results may provide a novel insight into the molecular mechanism involved in anti‐adipogenic and anti‐obesity effects of 18β‐GA by suppressing the activation of CB1R induced by AEA. Thus, 18β‐GA may exert beneficial effects against obesity‐related metabolic disorders.</description><identifier>ISSN: 1613-4125</identifier><identifier>EISSN: 1613-4133</identifier><identifier>DOI: 10.1002/mnfr.201300763</identifier><identifier>PMID: 24687644</identifier><language>eng</language><publisher>Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA</publisher><subject>18β-glycyrrhetinic acid ; 3T3-L1 ; 3T3-L1 Cells ; Acetyl-CoA Carboxylase - genetics ; Acetyl-CoA Carboxylase - metabolism ; active ingredients ; adipocytes ; Adipocytes - cytology ; Adipocytes - drug effects ; Adiposity ; agonists ; animal models ; Animals ; Arachidonic Acids - pharmacology ; Biological and medical sciences ; blood lipids ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - metabolism ; Body Weight - drug effects ; Cannabinoid receptor type 1 ; CCAAT-Enhancer-Binding Protein-alpha - genetics ; CCAAT-Enhancer-Binding Protein-alpha - metabolism ; Cell Differentiation - drug effects ; diet ; Diet, High-Fat - adverse effects ; Endocannabinoids - pharmacology ; fatty-acid synthase ; Feeding. Feeding behavior ; Fundamental and applied biological sciences. Psychology ; gene expression regulation ; genes ; Glycyrrhetinic Acid - analogs & derivatives ; Glycyrrhetinic Acid - pharmacology ; Glycyrrhiza - chemistry ; hyperlipidemia ; Licorice ; Lipids - blood ; Medical sciences ; Metabolic diseases ; Mice ; Mice, Inbred C57BL ; mitogen-activated protein kinase ; Neuropharmacology ; Obesity ; Obesity - chemically induced ; Obesity - metabolism ; Pharmacology. Drug treatments ; Phosphorylation ; Plant Extracts - pharmacology ; Polyunsaturated Alkamides - pharmacology ; PPAR gamma - genetics ; PPAR gamma - metabolism ; Psychodysleptics: hallucinogen ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Stearoyl-CoA Desaturase - genetics ; Stearoyl-CoA Desaturase - metabolism ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>Molecular nutrition & food research, 2014-07, Vol.58 (7), p.1436-1446</ispartof><rights>2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2015 INIST-CNRS</rights><rights>2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4538-9fa34e8a54e0464707cdc3e9f65309e6797a7bc42aad546a1002cc36ac9043493</citedby><cites>FETCH-LOGICAL-c4538-9fa34e8a54e0464707cdc3e9f65309e6797a7bc42aad546a1002cc36ac9043493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmnfr.201300763$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmnfr.201300763$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28583254$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24687644$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Miyoung</creatorcontrib><creatorcontrib>Lee, Ji‐Hae</creatorcontrib><creatorcontrib>Choi, Jin Kyu</creatorcontrib><creatorcontrib>Hong, Yong Deog</creatorcontrib><creatorcontrib>Bae, Il‐Hong</creatorcontrib><creatorcontrib>Lim, Kyung‐Min</creatorcontrib><creatorcontrib>Park, Young‐Ho</creatorcontrib><creatorcontrib>Ha, Hunjoo</creatorcontrib><title>18β‐glycyrrhetinic acid attenuates anandamide‐induced adiposity and high‐fat diet induced obesity</title><title>Molecular nutrition & food research</title><addtitle>Mol. Nutr. Food Res</addtitle><description>SCOPE: Previous reports suggest that licorice extract has various metabolically beneficial effects and may help to alleviate adiposity and hyperlipidemia. However, underlying anti‐obesity mechanisms still remain elusive. Moreover, it is unknown which single ingredient in licorice extract would mediate such effects. We aimed to demonstrate that licorice extract and its active ingredients can inhibit adipocyte differentiation and fat accumulation. METHODS AND RESULTS: 18β‐glycyrrhetinic acid (18β‐GA) alleviated the effects of CB1R agonist, anandamide (AEA) on CB1R signaling in a concentration‐dependent manner. Consistently, 18β‐GA suppressed AEA‐induced adipocyte differentiation in 3T3‐L1 cells through the downregulation of AEA‐induced MAPK activation and expression of adipogenic genes including C/EBP‐α and PPAR‐γ. The protein levels of fatty acid synthase and stearoyl‐CoA desaturase 1 were also decreased and the phosphorylation of acetyl‐CoA carboxylase was increased in 18β‐GA pretreated cells. The supplementation of 18β‐GA significantly lowered body weight, fat weight, and plasma lipids levels in obese animal models. CONCLUSION: These results may provide a novel insight into the molecular mechanism involved in anti‐adipogenic and anti‐obesity effects of 18β‐GA by suppressing the activation of CB1R induced by AEA. Thus, 18β‐GA may exert beneficial effects against obesity‐related metabolic disorders.</description><subject>18β-glycyrrhetinic acid</subject><subject>3T3-L1</subject><subject>3T3-L1 Cells</subject><subject>Acetyl-CoA Carboxylase - genetics</subject><subject>Acetyl-CoA Carboxylase - metabolism</subject><subject>active ingredients</subject><subject>adipocytes</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - drug effects</subject><subject>Adiposity</subject><subject>agonists</subject><subject>animal models</subject><subject>Animals</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Biological and medical sciences</subject><subject>blood lipids</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Body Weight - drug effects</subject><subject>Cannabinoid receptor type 1</subject><subject>CCAAT-Enhancer-Binding Protein-alpha - genetics</subject><subject>CCAAT-Enhancer-Binding Protein-alpha - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>diet</subject><subject>Diet, High-Fat - adverse effects</subject><subject>Endocannabinoids - pharmacology</subject><subject>fatty-acid synthase</subject><subject>Feeding. Feeding behavior</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gene expression regulation</subject><subject>genes</subject><subject>Glycyrrhetinic Acid - analogs & derivatives</subject><subject>Glycyrrhetinic Acid - pharmacology</subject><subject>Glycyrrhiza - chemistry</subject><subject>hyperlipidemia</subject><subject>Licorice</subject><subject>Lipids - blood</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>mitogen-activated protein kinase</subject><subject>Neuropharmacology</subject><subject>Obesity</subject><subject>Obesity - chemically induced</subject><subject>Obesity - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphorylation</subject><subject>Plant Extracts - pharmacology</subject><subject>Polyunsaturated Alkamides - pharmacology</subject><subject>PPAR gamma - genetics</subject><subject>PPAR gamma - metabolism</subject><subject>Psychodysleptics: hallucinogen</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Stearoyl-CoA Desaturase - genetics</subject><subject>Stearoyl-CoA Desaturase - metabolism</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>1613-4125</issn><issn>1613-4133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqF0E9u1DAUBvAIgWgpbFlCNkhsMvi_kyUd0YLUFglawc56Y7_MGDLJ1E4E2XEEzsJBOAQnwVGmw5KVLb3f92x9WfaUkgUlhL3atnVYMEI5IVrxe9kxVZQXgnJ-_3Bn8ih7FOMXQjhlgj_MjphQpVZCHGcbWv7-9efHz3Uz2jGEDfa-9TYH610OfY_tAD3GHFpoHWy9w2R96waLae78rou-H9PY5Ru_3qRhDX3uPPb5nepWOJnH2YMamohP9udJdnP25nr5trh4f_5u-fqisELysqhq4AJLkAKJUEITbZ3lWNVKclKh0pUGvbKCATgpFEwlWMsV2IoILip-kr2c9-5Cdztg7M3WR4tNAy12QzRUCsaqkjOZ6GKmNnQxBqzNLvgthNFQYqbFZmrXHNpNgWf73cNqi-7A7-pM4MUeQLTQ1AFa6-M_V8rp4cmJ2X3zDY7_edZcXp19YLQsU6yYYz72-P0Qg_DVKM21NJ-uzs3y8pRcn6rPZvLPZ19DZ2Ad0lduPqa9ghAqU9ua_wUoja8R</recordid><startdate>201407</startdate><enddate>201407</enddate><creator>Park, Miyoung</creator><creator>Lee, Ji‐Hae</creator><creator>Choi, Jin Kyu</creator><creator>Hong, Yong Deog</creator><creator>Bae, Il‐Hong</creator><creator>Lim, Kyung‐Min</creator><creator>Park, Young‐Ho</creator><creator>Ha, Hunjoo</creator><general>Wiley-VCH Verlag GmbH & Co. KGaA</general><general>Blackwell Publishing Ltd</general><general>Wiley</general><scope>FBQ</scope><scope>BSCLL</scope><scope>24P</scope><scope>WIN</scope><scope>IQODW</scope><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></search><sort><creationdate>201407</creationdate><title>18β‐glycyrrhetinic acid attenuates anandamide‐induced adiposity and high‐fat diet induced obesity</title><author>Park, Miyoung ; Lee, Ji‐Hae ; Choi, Jin Kyu ; Hong, Yong Deog ; Bae, Il‐Hong ; Lim, Kyung‐Min ; Park, Young‐Ho ; Ha, Hunjoo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4538-9fa34e8a54e0464707cdc3e9f65309e6797a7bc42aad546a1002cc36ac9043493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>18β-glycyrrhetinic acid</topic><topic>3T3-L1</topic><topic>3T3-L1 Cells</topic><topic>Acetyl-CoA Carboxylase - genetics</topic><topic>Acetyl-CoA Carboxylase - metabolism</topic><topic>active ingredients</topic><topic>adipocytes</topic><topic>Adipocytes - cytology</topic><topic>Adipocytes - drug effects</topic><topic>Adiposity</topic><topic>agonists</topic><topic>animal models</topic><topic>Animals</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Biological and medical sciences</topic><topic>blood lipids</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Body Weight - drug effects</topic><topic>Cannabinoid receptor type 1</topic><topic>CCAAT-Enhancer-Binding Protein-alpha - genetics</topic><topic>CCAAT-Enhancer-Binding Protein-alpha - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>diet</topic><topic>Diet, High-Fat - adverse effects</topic><topic>Endocannabinoids - pharmacology</topic><topic>fatty-acid synthase</topic><topic>Feeding. Feeding behavior</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>gene expression regulation</topic><topic>genes</topic><topic>Glycyrrhetinic Acid - analogs & derivatives</topic><topic>Glycyrrhetinic Acid - pharmacology</topic><topic>Glycyrrhiza - chemistry</topic><topic>hyperlipidemia</topic><topic>Licorice</topic><topic>Lipids - blood</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>mitogen-activated protein kinase</topic><topic>Neuropharmacology</topic><topic>Obesity</topic><topic>Obesity - chemically induced</topic><topic>Obesity - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphorylation</topic><topic>Plant Extracts - pharmacology</topic><topic>Polyunsaturated Alkamides - pharmacology</topic><topic>PPAR gamma - genetics</topic><topic>PPAR gamma - metabolism</topic><topic>Psychodysleptics: hallucinogen</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Stearoyl-CoA Desaturase - genetics</topic><topic>Stearoyl-CoA Desaturase - metabolism</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Miyoung</creatorcontrib><creatorcontrib>Lee, Ji‐Hae</creatorcontrib><creatorcontrib>Choi, Jin Kyu</creatorcontrib><creatorcontrib>Hong, Yong Deog</creatorcontrib><creatorcontrib>Bae, Il‐Hong</creatorcontrib><creatorcontrib>Lim, Kyung‐Min</creatorcontrib><creatorcontrib>Park, Young‐Ho</creatorcontrib><creatorcontrib>Ha, Hunjoo</creatorcontrib><collection>AGRIS</collection><collection>Istex</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library Free Content</collection><collection>Pascal-Francis</collection><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>Molecular nutrition & food research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Miyoung</au><au>Lee, Ji‐Hae</au><au>Choi, Jin Kyu</au><au>Hong, Yong Deog</au><au>Bae, Il‐Hong</au><au>Lim, Kyung‐Min</au><au>Park, Young‐Ho</au><au>Ha, Hunjoo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>18β‐glycyrrhetinic acid attenuates anandamide‐induced adiposity and high‐fat diet induced obesity</atitle><jtitle>Molecular nutrition & food research</jtitle><addtitle>Mol. Nutr. Food Res</addtitle><date>2014-07</date><risdate>2014</risdate><volume>58</volume><issue>7</issue><spage>1436</spage><epage>1446</epage><pages>1436-1446</pages><issn>1613-4125</issn><eissn>1613-4133</eissn><abstract>SCOPE: Previous reports suggest that licorice extract has various metabolically beneficial effects and may help to alleviate adiposity and hyperlipidemia. However, underlying anti‐obesity mechanisms still remain elusive. Moreover, it is unknown which single ingredient in licorice extract would mediate such effects. We aimed to demonstrate that licorice extract and its active ingredients can inhibit adipocyte differentiation and fat accumulation. METHODS AND RESULTS: 18β‐glycyrrhetinic acid (18β‐GA) alleviated the effects of CB1R agonist, anandamide (AEA) on CB1R signaling in a concentration‐dependent manner. Consistently, 18β‐GA suppressed AEA‐induced adipocyte differentiation in 3T3‐L1 cells through the downregulation of AEA‐induced MAPK activation and expression of adipogenic genes including C/EBP‐α and PPAR‐γ. The protein levels of fatty acid synthase and stearoyl‐CoA desaturase 1 were also decreased and the phosphorylation of acetyl‐CoA carboxylase was increased in 18β‐GA pretreated cells. The supplementation of 18β‐GA significantly lowered body weight, fat weight, and plasma lipids levels in obese animal models. CONCLUSION: These results may provide a novel insight into the molecular mechanism involved in anti‐adipogenic and anti‐obesity effects of 18β‐GA by suppressing the activation of CB1R induced by AEA. Thus, 18β‐GA may exert beneficial effects against obesity‐related metabolic disorders.</abstract><cop>Weinheim</cop><pub>Wiley-VCH Verlag GmbH & Co. KGaA</pub><pmid>24687644</pmid><doi>10.1002/mnfr.201300763</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular nutrition & food research, 2014-07, Vol.58 (7), p.1436-1446 |
| issn | 1613-4125 1613-4133 |
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| subjects | 18β-glycyrrhetinic acid 3T3-L1 3T3-L1 Cells Acetyl-CoA Carboxylase - genetics Acetyl-CoA Carboxylase - metabolism active ingredients adipocytes Adipocytes - cytology Adipocytes - drug effects Adiposity agonists animal models Animals Arachidonic Acids - pharmacology Biological and medical sciences blood lipids Blood-Brain Barrier - drug effects Blood-Brain Barrier - metabolism Body Weight - drug effects Cannabinoid receptor type 1 CCAAT-Enhancer-Binding Protein-alpha - genetics CCAAT-Enhancer-Binding Protein-alpha - metabolism Cell Differentiation - drug effects diet Diet, High-Fat - adverse effects Endocannabinoids - pharmacology fatty-acid synthase Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology gene expression regulation genes Glycyrrhetinic Acid - analogs & derivatives Glycyrrhetinic Acid - pharmacology Glycyrrhiza - chemistry hyperlipidemia Licorice Lipids - blood Medical sciences Metabolic diseases Mice Mice, Inbred C57BL mitogen-activated protein kinase Neuropharmacology Obesity Obesity - chemically induced Obesity - metabolism Pharmacology. Drug treatments Phosphorylation Plant Extracts - pharmacology Polyunsaturated Alkamides - pharmacology PPAR gamma - genetics PPAR gamma - metabolism Psychodysleptics: hallucinogen Psychology. Psychoanalysis. Psychiatry Psychopharmacology Stearoyl-CoA Desaturase - genetics Stearoyl-CoA Desaturase - metabolism Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| title | 18β‐glycyrrhetinic acid attenuates anandamide‐induced adiposity and high‐fat diet induced obesity |
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