Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective clearance of overloaded intermediates by exercise
Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia, hyperglycemia and insulin resistance, which correlated with high mortality worldwide. Exercise is one of the effective lifestyle interventions in maintaining blood glucose level in the normal range and lowering risk factors. Metab...
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| Veröffentlicht in: | Analytica chimica acta 2018-12, Vol.1037, p.130-139 |
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| creator | Xiang, Li Zhang, Hongsong Wei, Juntong Tian, Xiao Yu Luan, Hemi Li, Shangfu Zhao, Hongzhi Cao, Guodong Chung, Arthur C.K. Yang, Chunxue Huang, Yu Cai, Zongwei |
| description | Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia, hyperglycemia and insulin resistance, which correlated with high mortality worldwide. Exercise is one of the effective lifestyle interventions in maintaining blood glucose level in the normal range and lowering risk factors. Metabolomics approaches are powerful tools in systematic study of overall metabolic changes in response to disease or interventions. In this study, mass spectrometry-based metabolomics studies were performed to investigate the regulatory effect of moderate intensity of exercise on db/db diabetic mice in skeletal muscle. Both liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have been carried out to monitor a wide range of regulated metabolites. Ninety-five metabolites were identified which contributing to the discrimination of db/m + control and db/db diabetic mice. The regulatory effects of exercise on these metabolites were mainly focusing on attenuating the levels of long-chain fatty acids (C14 to C18) and medium-to long-chain acylcarnitines (C12 to C18), indicated that exercise might play a positive role in inhibiting the accumulation of excessive lipids, which is positively related to insulin resistance. In addition, uric acid, which is a risk factor for inflammation, cardiovascular complications, and fatty liver in diabetic patients, together with its intermediates (such as inosinic acid, hypoxanthine, etc.) in purine metabolism pathway, were also substantially down regulated after exercise, indicating exercise might also be protective against hyperuricemia related risks in T2DM. These findings reveal that moderate intensity of exercise might play a positive role in improving the efficiency of lipid metabolism in skeletal muscle and meanwhile enhancing uric acid clearance to prevent lipid accumulation, which might contribute to improved body fitness and body muscle composition.
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| doi_str_mv | 10.1016/j.aca.2017.11.082 |
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[Display omitted]</description><identifier>ISSN: 0003-2670</identifier><identifier>EISSN: 1873-4324</identifier><identifier>DOI: 10.1016/j.aca.2017.11.082</identifier><identifier>PMID: 30292287</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Accumulation ; Acid resistance ; Animals ; Blood glucose ; Cardiovascular diseases ; Chains ; Complications ; Db/db ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Type 2 - metabolism ; Exercise ; Fatty acids ; Fatty liver ; Fitness ; Gas chromatography ; Health risks ; Hyperglycemia ; Hyperinsulinemia ; Hyperuricemia ; Hypoxanthine ; Insulin ; Intermediates ; Lipid metabolism ; Lipids ; Liquid chromatography ; Liver ; Male ; Mass Spectrometry ; Mass spectroscopy ; Metabolism ; Metabolites ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal - metabolism ; Muscles ; Muscular system ; Physical Conditioning, Animal ; Physical fitness ; Risk analysis ; Risk factors ; Skeletal muscle ; Skeletal system ; Spectroscopy ; Uric acid</subject><ispartof>Analytica chimica acta, 2018-12, Vol.1037, p.130-139</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier BV Dec 11, 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-55e1ec2348370785f86361e9632a924b5b88ca139fb5b12b6d0adf9d17e866283</citedby><cites>FETCH-LOGICAL-c381t-55e1ec2348370785f86361e9632a924b5b88ca139fb5b12b6d0adf9d17e866283</cites><orcidid>0000-0002-8724-7684</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.aca.2017.11.082$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30292287$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiang, Li</creatorcontrib><creatorcontrib>Zhang, Hongsong</creatorcontrib><creatorcontrib>Wei, Juntong</creatorcontrib><creatorcontrib>Tian, Xiao Yu</creatorcontrib><creatorcontrib>Luan, Hemi</creatorcontrib><creatorcontrib>Li, Shangfu</creatorcontrib><creatorcontrib>Zhao, Hongzhi</creatorcontrib><creatorcontrib>Cao, Guodong</creatorcontrib><creatorcontrib>Chung, Arthur C.K.</creatorcontrib><creatorcontrib>Yang, Chunxue</creatorcontrib><creatorcontrib>Huang, Yu</creatorcontrib><creatorcontrib>Cai, Zongwei</creatorcontrib><title>Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective clearance of overloaded intermediates by exercise</title><title>Analytica chimica acta</title><addtitle>Anal Chim Acta</addtitle><description>Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia, hyperglycemia and insulin resistance, which correlated with high mortality worldwide. Exercise is one of the effective lifestyle interventions in maintaining blood glucose level in the normal range and lowering risk factors. Metabolomics approaches are powerful tools in systematic study of overall metabolic changes in response to disease or interventions. In this study, mass spectrometry-based metabolomics studies were performed to investigate the regulatory effect of moderate intensity of exercise on db/db diabetic mice in skeletal muscle. Both liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have been carried out to monitor a wide range of regulated metabolites. Ninety-five metabolites were identified which contributing to the discrimination of db/m + control and db/db diabetic mice. The regulatory effects of exercise on these metabolites were mainly focusing on attenuating the levels of long-chain fatty acids (C14 to C18) and medium-to long-chain acylcarnitines (C12 to C18), indicated that exercise might play a positive role in inhibiting the accumulation of excessive lipids, which is positively related to insulin resistance. In addition, uric acid, which is a risk factor for inflammation, cardiovascular complications, and fatty liver in diabetic patients, together with its intermediates (such as inosinic acid, hypoxanthine, etc.) in purine metabolism pathway, were also substantially down regulated after exercise, indicating exercise might also be protective against hyperuricemia related risks in T2DM. These findings reveal that moderate intensity of exercise might play a positive role in improving the efficiency of lipid metabolism in skeletal muscle and meanwhile enhancing uric acid clearance to prevent lipid accumulation, which might contribute to improved body fitness and body muscle composition.
[Display omitted]</description><subject>Accumulation</subject><subject>Acid resistance</subject><subject>Animals</subject><subject>Blood glucose</subject><subject>Cardiovascular diseases</subject><subject>Chains</subject><subject>Complications</subject><subject>Db/db</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Exercise</subject><subject>Fatty acids</subject><subject>Fatty liver</subject><subject>Fitness</subject><subject>Gas chromatography</subject><subject>Health risks</subject><subject>Hyperglycemia</subject><subject>Hyperinsulinemia</subject><subject>Hyperuricemia</subject><subject>Hypoxanthine</subject><subject>Insulin</subject><subject>Intermediates</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Liquid chromatography</subject><subject>Liver</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Mass spectroscopy</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscles</subject><subject>Muscular system</subject><subject>Physical Conditioning, Animal</subject><subject>Physical fitness</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Skeletal muscle</subject><subject>Skeletal system</subject><subject>Spectroscopy</subject><subject>Uric acid</subject><issn>0003-2670</issn><issn>1873-4324</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kTFv1TAUhS1E1b6W_gAWZImFJamvncSOmFAFFKkVC8yWY99IfiRxsZOnduSfc6tXGBiY7Gt_59g6h7HXIGoQ0F3ta-ddLQXoGqAWRr5gOzBaVY2SzUu2E0KoSnZanLHzUvY0ShDNKTtTQvZSGr1jv-5wdUOa0hx94WXdQsTC08LDcBUGHqIbcI2e0zXyuPDyAydSTHzeip-QZzwgTTiO6Nd4QE6HLruF6DTydMA8JRcwkHbFPCMZrvTA8MjxAbOPBV-xk9FNBS-f1wv2_dPHb9c31e3Xz1-uP9xWXhlYq7ZFQC9VY5QW2rSj6VQH2HdKul42QzsY4x2ofqQtyKELwoWxD6DRdJ006oK9O_re5_Rzw7LaORaP0-QWTFuxEkBD27RNR-jbf9B92vJCvyOqMX2rlVZEwZHyOZWScbT3Oc4uP1oQ9qkfu7fUj33qxwJY6oc0b56dt4HC-Kv4UwgB748AUhSHiNkWH5HiDDFTwjak-B_730yloK4</recordid><startdate>20181211</startdate><enddate>20181211</enddate><creator>Xiang, Li</creator><creator>Zhang, Hongsong</creator><creator>Wei, Juntong</creator><creator>Tian, Xiao Yu</creator><creator>Luan, Hemi</creator><creator>Li, Shangfu</creator><creator>Zhao, Hongzhi</creator><creator>Cao, Guodong</creator><creator>Chung, Arthur C.K.</creator><creator>Yang, Chunxue</creator><creator>Huang, Yu</creator><creator>Cai, Zongwei</creator><general>Elsevier B.V</general><general>Elsevier BV</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>7QF</scope><scope>7QO</scope><scope>7QP</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8724-7684</orcidid></search><sort><creationdate>20181211</creationdate><title>Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective clearance of overloaded intermediates by exercise</title><author>Xiang, Li ; Zhang, Hongsong ; Wei, Juntong ; Tian, Xiao Yu ; Luan, Hemi ; Li, Shangfu ; Zhao, Hongzhi ; Cao, Guodong ; Chung, Arthur C.K. ; Yang, Chunxue ; Huang, Yu ; Cai, Zongwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-55e1ec2348370785f86361e9632a924b5b88ca139fb5b12b6d0adf9d17e866283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Accumulation</topic><topic>Acid resistance</topic><topic>Animals</topic><topic>Blood glucose</topic><topic>Cardiovascular diseases</topic><topic>Chains</topic><topic>Complications</topic><topic>Db/db</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Exercise</topic><topic>Fatty acids</topic><topic>Fatty liver</topic><topic>Fitness</topic><topic>Gas chromatography</topic><topic>Health risks</topic><topic>Hyperglycemia</topic><topic>Hyperinsulinemia</topic><topic>Hyperuricemia</topic><topic>Hypoxanthine</topic><topic>Insulin</topic><topic>Intermediates</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Liquid chromatography</topic><topic>Liver</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Mass spectroscopy</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolomics</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscles</topic><topic>Muscular system</topic><topic>Physical Conditioning, Animal</topic><topic>Physical fitness</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Skeletal muscle</topic><topic>Skeletal system</topic><topic>Spectroscopy</topic><topic>Uric acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xiang, Li</creatorcontrib><creatorcontrib>Zhang, Hongsong</creatorcontrib><creatorcontrib>Wei, Juntong</creatorcontrib><creatorcontrib>Tian, Xiao Yu</creatorcontrib><creatorcontrib>Luan, Hemi</creatorcontrib><creatorcontrib>Li, Shangfu</creatorcontrib><creatorcontrib>Zhao, Hongzhi</creatorcontrib><creatorcontrib>Cao, Guodong</creatorcontrib><creatorcontrib>Chung, Arthur C.K.</creatorcontrib><creatorcontrib>Yang, Chunxue</creatorcontrib><creatorcontrib>Huang, Yu</creatorcontrib><creatorcontrib>Cai, Zongwei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Analytica chimica acta</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiang, Li</au><au>Zhang, Hongsong</au><au>Wei, Juntong</au><au>Tian, Xiao Yu</au><au>Luan, Hemi</au><au>Li, Shangfu</au><au>Zhao, Hongzhi</au><au>Cao, Guodong</au><au>Chung, Arthur C.K.</au><au>Yang, Chunxue</au><au>Huang, Yu</au><au>Cai, Zongwei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective clearance of overloaded intermediates by exercise</atitle><jtitle>Analytica chimica acta</jtitle><addtitle>Anal Chim Acta</addtitle><date>2018-12-11</date><risdate>2018</risdate><volume>1037</volume><spage>130</spage><epage>139</epage><pages>130-139</pages><issn>0003-2670</issn><eissn>1873-4324</eissn><abstract>Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia, hyperglycemia and insulin resistance, which correlated with high mortality worldwide. Exercise is one of the effective lifestyle interventions in maintaining blood glucose level in the normal range and lowering risk factors. Metabolomics approaches are powerful tools in systematic study of overall metabolic changes in response to disease or interventions. In this study, mass spectrometry-based metabolomics studies were performed to investigate the regulatory effect of moderate intensity of exercise on db/db diabetic mice in skeletal muscle. Both liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have been carried out to monitor a wide range of regulated metabolites. Ninety-five metabolites were identified which contributing to the discrimination of db/m + control and db/db diabetic mice. The regulatory effects of exercise on these metabolites were mainly focusing on attenuating the levels of long-chain fatty acids (C14 to C18) and medium-to long-chain acylcarnitines (C12 to C18), indicated that exercise might play a positive role in inhibiting the accumulation of excessive lipids, which is positively related to insulin resistance. In addition, uric acid, which is a risk factor for inflammation, cardiovascular complications, and fatty liver in diabetic patients, together with its intermediates (such as inosinic acid, hypoxanthine, etc.) in purine metabolism pathway, were also substantially down regulated after exercise, indicating exercise might also be protective against hyperuricemia related risks in T2DM. These findings reveal that moderate intensity of exercise might play a positive role in improving the efficiency of lipid metabolism in skeletal muscle and meanwhile enhancing uric acid clearance to prevent lipid accumulation, which might contribute to improved body fitness and body muscle composition.
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| subjects | Accumulation Acid resistance Animals Blood glucose Cardiovascular diseases Chains Complications Db/db Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Type 2 - metabolism Exercise Fatty acids Fatty liver Fitness Gas chromatography Health risks Hyperglycemia Hyperinsulinemia Hyperuricemia Hypoxanthine Insulin Intermediates Lipid metabolism Lipids Liquid chromatography Liver Male Mass Spectrometry Mass spectroscopy Metabolism Metabolites Metabolomics Mice Mice, Inbred C57BL Muscle, Skeletal - metabolism Muscles Muscular system Physical Conditioning, Animal Physical fitness Risk analysis Risk factors Skeletal muscle Skeletal system Spectroscopy Uric acid |
| title | Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective clearance of overloaded intermediates by exercise |
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