Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women
Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were di...
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| Veröffentlicht in: | Scientific reports 2016-04, Vol.6 (1), p.24540-24540, Article 24540 |
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| creator | Wiklund, Petri Zhang, Xiaobo Pekkala, Satu Autio, Reija Kong, Lingjia Yang, Yifan Keinänen-Kiukaanniemi, Sirkka Alen, Markku Cheng, Sulin |
| description | Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p |
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In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p < 0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep24540</identifier><identifier>PMID: 27080554</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>140/131 ; 38/39 ; 631/443/319 ; 692/53/2423 ; Adipose tissue ; Adipose Tissue - metabolism ; Amino acids ; Amino Acids - metabolism ; Anthropometry ; Blood Glucose ; Body Composition ; DNA microarrays ; Dual energy X-ray absorptiometry ; Energy metabolism ; Female ; Gene Expression ; Gene regulation ; Humanities and Social Sciences ; Humans ; Inflammation - genetics ; Inflammation - metabolism ; Insulin ; Insulin Resistance ; Liver ; Magnetic resonance spectroscopy ; Metabolism ; Metabolites ; Mitochondria ; multidisciplinary ; Muscle, Skeletal - metabolism ; Musculoskeletal system ; NMR ; Nuclear magnetic resonance ; Phosphorylation ; Science ; Science (multidisciplinary) ; Signal Transduction ; Skeletal muscle ; Spectroscopy ; Spectrum analysis ; Subcutaneous Fat - metabolism</subject><ispartof>Scientific reports, 2016-04, Vol.6 (1), p.24540-24540, Article 24540</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Apr 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-15de8d916a2ba1670744257ee64ea36451e6b25766d794aa48041a26855720e33</citedby><cites>FETCH-LOGICAL-c438t-15de8d916a2ba1670744257ee64ea36451e6b25766d794aa48041a26855720e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832240/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832240/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,41101,42170,51557,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27080554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wiklund, Petri</creatorcontrib><creatorcontrib>Zhang, Xiaobo</creatorcontrib><creatorcontrib>Pekkala, Satu</creatorcontrib><creatorcontrib>Autio, Reija</creatorcontrib><creatorcontrib>Kong, Lingjia</creatorcontrib><creatorcontrib>Yang, Yifan</creatorcontrib><creatorcontrib>Keinänen-Kiukaanniemi, Sirkka</creatorcontrib><creatorcontrib>Alen, Markku</creatorcontrib><creatorcontrib>Cheng, Sulin</creatorcontrib><title>Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p < 0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue.</description><subject>140/131</subject><subject>38/39</subject><subject>631/443/319</subject><subject>692/53/2423</subject><subject>Adipose tissue</subject><subject>Adipose Tissue - metabolism</subject><subject>Amino acids</subject><subject>Amino Acids - metabolism</subject><subject>Anthropometry</subject><subject>Blood Glucose</subject><subject>Body Composition</subject><subject>DNA microarrays</subject><subject>Dual energy X-ray absorptiometry</subject><subject>Energy metabolism</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene regulation</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Inflammation - genetics</subject><subject>Inflammation - metabolism</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Liver</subject><subject>Magnetic resonance spectroscopy</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Mitochondria</subject><subject>multidisciplinary</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Musculoskeletal system</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Phosphorylation</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal Transduction</subject><subject>Skeletal muscle</subject><subject>Spectroscopy</subject><subject>Spectrum analysis</subject><subject>Subcutaneous Fat - metabolism</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkV1rFDEUhgex2FJ74R-QgDdaWJtkkkzmRpBitVDoTb0OZzNntykzyZqTadl_b8rWZdXc5OM8PDnJ2zTvBP8seGsvKONGKq34q-ZEcqUXspXy9cH6uDkjeuB1aNkr0b9pjmXHLddanTTb60jzGCLLSIEKRI8sEAOi5AMUHNhTKPcMxoK5bmAKMTHwYWATFlimMdDEINbKEDaJkJVANCMbtrSaoy8hRVbtMeUprcetxyl49pQmjG-boxWMhGcv82nz8-rb3eWPxc3t9-vLrzcLr1pbFkIPaIdeGJBLEKbjnVJSd4hGIbRGaYFmWQ-MGbpeASjLlQBprNad5Ni2p82XnXczLyccPMaSYXSbHCbIW5cguL8rMdy7dXp0ytbPU7wKPr4Icvo1IxU3BfI4jhAxzeREZ4VubWue0Q__oA9pzrE-zwnbW2Orr6vUpx3lc6Ia32rfjODuOVO3z7Sy7w-735N_EqzA-Q6gWoprzAdX_mf7DRD1rLo</recordid><startdate>20160415</startdate><enddate>20160415</enddate><creator>Wiklund, Petri</creator><creator>Zhang, Xiaobo</creator><creator>Pekkala, Satu</creator><creator>Autio, Reija</creator><creator>Kong, Lingjia</creator><creator>Yang, Yifan</creator><creator>Keinänen-Kiukaanniemi, Sirkka</creator><creator>Alen, Markku</creator><creator>Cheng, Sulin</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160415</creationdate><title>Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women</title><author>Wiklund, Petri ; Zhang, Xiaobo ; Pekkala, Satu ; Autio, Reija ; Kong, Lingjia ; Yang, Yifan ; Keinänen-Kiukaanniemi, Sirkka ; Alen, Markku ; Cheng, Sulin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-15de8d916a2ba1670744257ee64ea36451e6b25766d794aa48041a26855720e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>140/131</topic><topic>38/39</topic><topic>631/443/319</topic><topic>692/53/2423</topic><topic>Adipose tissue</topic><topic>Adipose Tissue - metabolism</topic><topic>Amino acids</topic><topic>Amino Acids - metabolism</topic><topic>Anthropometry</topic><topic>Blood Glucose</topic><topic>Body Composition</topic><topic>DNA microarrays</topic><topic>Dual energy X-ray absorptiometry</topic><topic>Energy metabolism</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gene regulation</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Inflammation - genetics</topic><topic>Inflammation - metabolism</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Liver</topic><topic>Magnetic resonance spectroscopy</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Mitochondria</topic><topic>multidisciplinary</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Musculoskeletal system</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Phosphorylation</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal Transduction</topic><topic>Skeletal muscle</topic><topic>Spectroscopy</topic><topic>Spectrum analysis</topic><topic>Subcutaneous Fat - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wiklund, Petri</creatorcontrib><creatorcontrib>Zhang, Xiaobo</creatorcontrib><creatorcontrib>Pekkala, Satu</creatorcontrib><creatorcontrib>Autio, Reija</creatorcontrib><creatorcontrib>Kong, Lingjia</creatorcontrib><creatorcontrib>Yang, Yifan</creatorcontrib><creatorcontrib>Keinänen-Kiukaanniemi, Sirkka</creatorcontrib><creatorcontrib>Alen, Markku</creatorcontrib><creatorcontrib>Cheng, Sulin</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wiklund, Petri</au><au>Zhang, Xiaobo</au><au>Pekkala, Satu</au><au>Autio, Reija</au><au>Kong, Lingjia</au><au>Yang, Yifan</au><au>Keinänen-Kiukaanniemi, Sirkka</au><au>Alen, Markku</au><au>Cheng, Sulin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-04-15</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>24540</spage><epage>24540</epage><pages>24540-24540</pages><artnum>24540</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p < 0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27080554</pmid><doi>10.1038/srep24540</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 140/131 38/39 631/443/319 692/53/2423 Adipose tissue Adipose Tissue - metabolism Amino acids Amino Acids - metabolism Anthropometry Blood Glucose Body Composition DNA microarrays Dual energy X-ray absorptiometry Energy metabolism Female Gene Expression Gene regulation Humanities and Social Sciences Humans Inflammation - genetics Inflammation - metabolism Insulin Insulin Resistance Liver Magnetic resonance spectroscopy Metabolism Metabolites Mitochondria multidisciplinary Muscle, Skeletal - metabolism Musculoskeletal system NMR Nuclear magnetic resonance Phosphorylation Science Science (multidisciplinary) Signal Transduction Skeletal muscle Spectroscopy Spectrum analysis Subcutaneous Fat - metabolism |
| title | Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women |
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