Ether lipids, sphingolipids and toxic 1‐deoxyceramides as hallmarks for lean and obese type 2 diabetic patients
Aim The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phe...
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| Veröffentlicht in: | Acta Physiologica 2021-05, Vol.232 (1), p.e13610-n/a |
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| creator | Hannich, J. Thomas Loizides‐Mangold, Ursula Sinturel, Flore Harayama, Takeshi Vandereycken, Bart Saini, Camille Gosselin, Pauline Brulhart‐Meynet, Marie‐Claude Robert, Maud Chanon, Stephanie Durand, Christine Paz Montoya, Jonathan David, Fabrice P. A. Guessous, Idris Pataky, Zoltan Golay, Alain Jornayvaz, François R. Philippe, Jacques Dermitzakis, Emmanouil T. Brown, Steven A. Lefai, Etienne Riezman, Howard Dibner, Charna |
| description | Aim
The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype.
Methods
To better understand the complex metabolic pattern of lean and obese T2D and non‐T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry‐based lipid analysis.
Results
Lipid homeostasis was strongly altered in a disease‐ and tissue‐specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso‐, diacyl‐ and ether‐phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1‐deoxyceramide accumulation in a disease‐specific manner in serum and visceral adipose tissue. The high amounts of non‐canonical 1‐deoxyceramide present in human adipose tissue most likely come from cell‐autonomous synthesis because 1‐deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments.
Conclusion
Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes. |
| doi_str_mv | 10.1111/apha.13610 |
| format | Article |
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The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype.
Methods
To better understand the complex metabolic pattern of lean and obese T2D and non‐T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry‐based lipid analysis.
Results
Lipid homeostasis was strongly altered in a disease‐ and tissue‐specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso‐, diacyl‐ and ether‐phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1‐deoxyceramide accumulation in a disease‐specific manner in serum and visceral adipose tissue. The high amounts of non‐canonical 1‐deoxyceramide present in human adipose tissue most likely come from cell‐autonomous synthesis because 1‐deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments.
Conclusion
Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.</description><identifier>ISSN: 1748-1708</identifier><identifier>EISSN: 1748-1716</identifier><identifier>DOI: 10.1111/apha.13610</identifier><identifier>PMID: 33351229</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>1‐deoxyceramide ; Adipocytes ; Adipose tissue ; Cell culture ; Cell differentiation ; Cytotoxicity ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Homeostasis ; Life Sciences ; lipid metabolism ; lipidomics ; Lipids ; Mass spectroscopy ; Obesity ; Phenotypes ; Phospholipids ; Precision medicine ; serum ; Skeletal muscle ; Sphingolipids ; Type 2 diabetes in lean and obese subjects ; visceral adipose tissue</subject><ispartof>Acta Physiologica, 2021-05, Vol.232 (1), p.e13610-n/a</ispartof><rights>2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd</rights><rights>2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2021 Scandinavian Physiological Society</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3940-d2bbe3ed5de3c36e797af53bae755975044e9fb1d2480009c1bd12cc773f91dd3</citedby><cites>FETCH-LOGICAL-c3940-d2bbe3ed5de3c36e797af53bae755975044e9fb1d2480009c1bd12cc773f91dd3</cites><orcidid>0000-0002-4188-803X ; 0000-0002-3042-7801 ; 0000-0003-4680-9422 ; 0000-0001-8539-865X ; 0000-0001-9233-2974 ; 0000-0003-2255-4197 ; 0000-0002-9302-6490 ; 0000-0002-8720-3833 ; 0000-0002-2286-4956 ; 0000-0001-9425-3137 ; 0000-0003-3210-0113 ; 0000-0001-6930-6671</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fapha.13610$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fapha.13610$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33351229$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-03269069$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Hannich, J. Thomas</creatorcontrib><creatorcontrib>Loizides‐Mangold, Ursula</creatorcontrib><creatorcontrib>Sinturel, Flore</creatorcontrib><creatorcontrib>Harayama, Takeshi</creatorcontrib><creatorcontrib>Vandereycken, Bart</creatorcontrib><creatorcontrib>Saini, Camille</creatorcontrib><creatorcontrib>Gosselin, Pauline</creatorcontrib><creatorcontrib>Brulhart‐Meynet, Marie‐Claude</creatorcontrib><creatorcontrib>Robert, Maud</creatorcontrib><creatorcontrib>Chanon, Stephanie</creatorcontrib><creatorcontrib>Durand, Christine</creatorcontrib><creatorcontrib>Paz Montoya, Jonathan</creatorcontrib><creatorcontrib>David, Fabrice P. A.</creatorcontrib><creatorcontrib>Guessous, Idris</creatorcontrib><creatorcontrib>Pataky, Zoltan</creatorcontrib><creatorcontrib>Golay, Alain</creatorcontrib><creatorcontrib>Jornayvaz, François R.</creatorcontrib><creatorcontrib>Philippe, Jacques</creatorcontrib><creatorcontrib>Dermitzakis, Emmanouil T.</creatorcontrib><creatorcontrib>Brown, Steven A.</creatorcontrib><creatorcontrib>Lefai, Etienne</creatorcontrib><creatorcontrib>Riezman, Howard</creatorcontrib><creatorcontrib>Dibner, Charna</creatorcontrib><title>Ether lipids, sphingolipids and toxic 1‐deoxyceramides as hallmarks for lean and obese type 2 diabetic patients</title><title>Acta Physiologica</title><addtitle>Acta Physiol (Oxf)</addtitle><description>Aim
The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype.
Methods
To better understand the complex metabolic pattern of lean and obese T2D and non‐T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry‐based lipid analysis.
Results
Lipid homeostasis was strongly altered in a disease‐ and tissue‐specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso‐, diacyl‐ and ether‐phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1‐deoxyceramide accumulation in a disease‐specific manner in serum and visceral adipose tissue. The high amounts of non‐canonical 1‐deoxyceramide present in human adipose tissue most likely come from cell‐autonomous synthesis because 1‐deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments.
Conclusion
Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.</description><subject>1‐deoxyceramide</subject><subject>Adipocytes</subject><subject>Adipose tissue</subject><subject>Cell culture</subject><subject>Cell differentiation</subject><subject>Cytotoxicity</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Homeostasis</subject><subject>Life Sciences</subject><subject>lipid metabolism</subject><subject>lipidomics</subject><subject>Lipids</subject><subject>Mass spectroscopy</subject><subject>Obesity</subject><subject>Phenotypes</subject><subject>Phospholipids</subject><subject>Precision medicine</subject><subject>serum</subject><subject>Skeletal muscle</subject><subject>Sphingolipids</subject><subject>Type 2 diabetes in lean and obese subjects</subject><subject>visceral adipose tissue</subject><issn>1748-1708</issn><issn>1748-1716</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kc1OAyEURonRqFE3PoAhcWescmF-yrIx1Zo00YWuCTPcseh0GGGqducj-Iw-ibSjXcoGCIeTDz5CjoFdQByXup3pCxAZsC2yD3kyHEAO2fZmzYZ75CiEZ8YYcBAJ57tkTwiRAudyn7yOuxl6WtvWmnBOQzuzzZPrt1Q3hnbuw5YUvj-_DLqPZYlez63BeBjoTNf1XPuXQCsXHaib9RVXYEDaLVuknBqrC-yiotWdxaYLh2Sn0nXAo9_5gDxejx-uJoPp3c3t1Wg6KIVM2MDwokCBJjUoSpFhLnNdpaLQmKepzFOWJCirAgxPhvFtsoTCAC_LPBeVBGPEATnvvTGlar2NQZfKaasmo6myTUA_V0zwTLJMvkHET3u89e51gaFTz27hm5hQ8VTwhKVZwiJ11lOldyF4rDZmYGrVh1r1odZ9RPjkV7ko5mg26N_vRwB64N3WuPxHpUb3k1Ev_QEEN5Xc</recordid><startdate>202105</startdate><enddate>202105</enddate><creator>Hannich, J. Thomas</creator><creator>Loizides‐Mangold, Ursula</creator><creator>Sinturel, Flore</creator><creator>Harayama, Takeshi</creator><creator>Vandereycken, Bart</creator><creator>Saini, Camille</creator><creator>Gosselin, Pauline</creator><creator>Brulhart‐Meynet, Marie‐Claude</creator><creator>Robert, Maud</creator><creator>Chanon, Stephanie</creator><creator>Durand, Christine</creator><creator>Paz Montoya, Jonathan</creator><creator>David, Fabrice P. A.</creator><creator>Guessous, Idris</creator><creator>Pataky, Zoltan</creator><creator>Golay, Alain</creator><creator>Jornayvaz, François R.</creator><creator>Philippe, Jacques</creator><creator>Dermitzakis, Emmanouil T.</creator><creator>Brown, Steven A.</creator><creator>Lefai, Etienne</creator><creator>Riezman, Howard</creator><creator>Dibner, Charna</creator><general>Wiley Subscription Services, Inc</general><general>Wiley</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TS</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-4188-803X</orcidid><orcidid>https://orcid.org/0000-0002-3042-7801</orcidid><orcidid>https://orcid.org/0000-0003-4680-9422</orcidid><orcidid>https://orcid.org/0000-0001-8539-865X</orcidid><orcidid>https://orcid.org/0000-0001-9233-2974</orcidid><orcidid>https://orcid.org/0000-0003-2255-4197</orcidid><orcidid>https://orcid.org/0000-0002-9302-6490</orcidid><orcidid>https://orcid.org/0000-0002-8720-3833</orcidid><orcidid>https://orcid.org/0000-0002-2286-4956</orcidid><orcidid>https://orcid.org/0000-0001-9425-3137</orcidid><orcidid>https://orcid.org/0000-0003-3210-0113</orcidid><orcidid>https://orcid.org/0000-0001-6930-6671</orcidid></search><sort><creationdate>202105</creationdate><title>Ether lipids, sphingolipids and toxic 1‐deoxyceramides as hallmarks for lean and obese type 2 diabetic patients</title><author>Hannich, J. Thomas ; Loizides‐Mangold, Ursula ; Sinturel, Flore ; Harayama, Takeshi ; Vandereycken, Bart ; Saini, Camille ; Gosselin, Pauline ; Brulhart‐Meynet, Marie‐Claude ; Robert, Maud ; Chanon, Stephanie ; Durand, Christine ; Paz Montoya, Jonathan ; David, Fabrice P. A. ; Guessous, Idris ; Pataky, Zoltan ; Golay, Alain ; Jornayvaz, François R. ; Philippe, Jacques ; Dermitzakis, Emmanouil T. ; Brown, Steven A. ; Lefai, Etienne ; Riezman, Howard ; Dibner, Charna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3940-d2bbe3ed5de3c36e797af53bae755975044e9fb1d2480009c1bd12cc773f91dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>1‐deoxyceramide</topic><topic>Adipocytes</topic><topic>Adipose tissue</topic><topic>Cell culture</topic><topic>Cell differentiation</topic><topic>Cytotoxicity</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Homeostasis</topic><topic>Life Sciences</topic><topic>lipid metabolism</topic><topic>lipidomics</topic><topic>Lipids</topic><topic>Mass spectroscopy</topic><topic>Obesity</topic><topic>Phenotypes</topic><topic>Phospholipids</topic><topic>Precision medicine</topic><topic>serum</topic><topic>Skeletal muscle</topic><topic>Sphingolipids</topic><topic>Type 2 diabetes in lean and obese subjects</topic><topic>visceral adipose tissue</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hannich, J. Thomas</creatorcontrib><creatorcontrib>Loizides‐Mangold, Ursula</creatorcontrib><creatorcontrib>Sinturel, Flore</creatorcontrib><creatorcontrib>Harayama, Takeshi</creatorcontrib><creatorcontrib>Vandereycken, Bart</creatorcontrib><creatorcontrib>Saini, Camille</creatorcontrib><creatorcontrib>Gosselin, Pauline</creatorcontrib><creatorcontrib>Brulhart‐Meynet, Marie‐Claude</creatorcontrib><creatorcontrib>Robert, Maud</creatorcontrib><creatorcontrib>Chanon, Stephanie</creatorcontrib><creatorcontrib>Durand, Christine</creatorcontrib><creatorcontrib>Paz Montoya, Jonathan</creatorcontrib><creatorcontrib>David, Fabrice P. A.</creatorcontrib><creatorcontrib>Guessous, Idris</creatorcontrib><creatorcontrib>Pataky, Zoltan</creatorcontrib><creatorcontrib>Golay, Alain</creatorcontrib><creatorcontrib>Jornayvaz, François R.</creatorcontrib><creatorcontrib>Philippe, Jacques</creatorcontrib><creatorcontrib>Dermitzakis, Emmanouil T.</creatorcontrib><creatorcontrib>Brown, Steven A.</creatorcontrib><creatorcontrib>Lefai, Etienne</creatorcontrib><creatorcontrib>Riezman, Howard</creatorcontrib><creatorcontrib>Dibner, Charna</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Acta Physiologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hannich, J. Thomas</au><au>Loizides‐Mangold, Ursula</au><au>Sinturel, Flore</au><au>Harayama, Takeshi</au><au>Vandereycken, Bart</au><au>Saini, Camille</au><au>Gosselin, Pauline</au><au>Brulhart‐Meynet, Marie‐Claude</au><au>Robert, Maud</au><au>Chanon, Stephanie</au><au>Durand, Christine</au><au>Paz Montoya, Jonathan</au><au>David, Fabrice P. A.</au><au>Guessous, Idris</au><au>Pataky, Zoltan</au><au>Golay, Alain</au><au>Jornayvaz, François R.</au><au>Philippe, Jacques</au><au>Dermitzakis, Emmanouil T.</au><au>Brown, Steven A.</au><au>Lefai, Etienne</au><au>Riezman, Howard</au><au>Dibner, Charna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ether lipids, sphingolipids and toxic 1‐deoxyceramides as hallmarks for lean and obese type 2 diabetic patients</atitle><jtitle>Acta Physiologica</jtitle><addtitle>Acta Physiol (Oxf)</addtitle><date>2021-05</date><risdate>2021</risdate><volume>232</volume><issue>1</issue><spage>e13610</spage><epage>n/a</epage><pages>e13610-n/a</pages><issn>1748-1708</issn><eissn>1748-1716</eissn><abstract>Aim
The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype.
Methods
To better understand the complex metabolic pattern of lean and obese T2D and non‐T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry‐based lipid analysis.
Results
Lipid homeostasis was strongly altered in a disease‐ and tissue‐specific manner, allowing us to define T2D signatures associated with obesity from those that were obesity independent. Lipid changes encompassed lyso‐, diacyl‐ and ether‐phospholipids. Moreover, strong changes in sphingolipids included cytotoxic 1‐deoxyceramide accumulation in a disease‐specific manner in serum and visceral adipose tissue. The high amounts of non‐canonical 1‐deoxyceramide present in human adipose tissue most likely come from cell‐autonomous synthesis because 1‐deoxyceramide production increased upon differentiation to adipocytes in mouse cell culture experiments.
Conclusion
Taken together, the observed lipidome changes in obesity and T2D will facilitate the identification of T2D patient subgroups and represent an important step towards personalized medicine in diabetes.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33351229</pmid><doi>10.1111/apha.13610</doi><tpages>20</tpages><orcidid>https://orcid.org/0000-0002-4188-803X</orcidid><orcidid>https://orcid.org/0000-0002-3042-7801</orcidid><orcidid>https://orcid.org/0000-0003-4680-9422</orcidid><orcidid>https://orcid.org/0000-0001-8539-865X</orcidid><orcidid>https://orcid.org/0000-0001-9233-2974</orcidid><orcidid>https://orcid.org/0000-0003-2255-4197</orcidid><orcidid>https://orcid.org/0000-0002-9302-6490</orcidid><orcidid>https://orcid.org/0000-0002-8720-3833</orcidid><orcidid>https://orcid.org/0000-0002-2286-4956</orcidid><orcidid>https://orcid.org/0000-0001-9425-3137</orcidid><orcidid>https://orcid.org/0000-0003-3210-0113</orcidid><orcidid>https://orcid.org/0000-0001-6930-6671</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Access via Wiley Online Library |
| subjects | 1‐deoxyceramide Adipocytes Adipose tissue Cell culture Cell differentiation Cytotoxicity Diabetes Diabetes mellitus (non-insulin dependent) Homeostasis Life Sciences lipid metabolism lipidomics Lipids Mass spectroscopy Obesity Phenotypes Phospholipids Precision medicine serum Skeletal muscle Sphingolipids Type 2 diabetes in lean and obese subjects visceral adipose tissue |
| title | Ether lipids, sphingolipids and toxic 1‐deoxyceramides as hallmarks for lean and obese type 2 diabetic patients |
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