Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity
Aim/hypothesis Altered adipose tissue secretory profile contributes to insulin resistance and type 2 diabetes in obesity. Preclinical studies have identified senescent cells as a cellular source of proinflammatory factors in adipose tissue of obese mice. In humans, potential links with obesity comor...
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| Veröffentlicht in: | Diabetologia 2021-01, Vol.64 (1), p.240-254 |
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| creator | Rouault, Christine Marcelin, Geneviève Adriouch, Solia Rose, Cindy Genser, Laurent Ambrosini, Marc Bichet, Jean-Christophe Zhang, Yanyan Marquet, Florian Aron-Wisnewsky, Judith Poitou, Christine André, Sébastien Dérumeaux, Geneviève Guerre-Millo, Michèle Clément, Karine |
| description | Aim/hypothesis
Altered adipose tissue secretory profile contributes to insulin resistance and type 2 diabetes in obesity. Preclinical studies have identified senescent cells as a cellular source of proinflammatory factors in adipose tissue of obese mice. In humans, potential links with obesity comorbidities are poorly defined. Here, we investigated adipose tissue senescent status and relationships with metabolic complications in human obesity.
Methods
The study includes a prospective cohort of 227 individuals with severe obesity. A photometric method was used to quantify senescence-associated β-galactosidase (SA-β-gal) activity in paired subcutaneous and omental adipose tissue biopsies obtained during gastric surgery. Gene and secretory profiling was performed in adipose tissue biopsies and in human primary pre-adipocytes in the presence or absence of senolytic drugs targeting senescent cells. Participants were phenotyped for anthropometric and bioclinical variables, metabolic complications and gastric surgery-induced improvement to address relationships with adipose tissue SA-β-gal.
Results
SA-β-gal activity was sevenfold higher in subcutaneous than in omental adipose tissue and not associated with BMI or chronological age. Several factors, including insulin-like growth factor binding protein 3 (IGFBP3), plasminogen activator inhibitor 1 (PAI1), C–C motif chemokine ligand 2 (CCL2) and IL-6, were upregulated in subcutaneous adipose tissue in relation with SA-β-gal (
p
for linear trend across tertiles |
| doi_str_mv | 10.1007/s00125-020-05307-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_04000945v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2456410728</sourcerecordid><originalsourceid>FETCH-LOGICAL-c453t-2df8a39865a2c3a15169ba8942c524b325e80369956d2299eddf20043ab929a3</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhS0EokPhBVggS2zKInD9l4mXVQUUaSQWdMHOunGcqatMMuQ6reYteJY-CM-E05RBYsHK0r3fObbPYey1gPcCYP2BAIQ0BUgowChYF_CErYRWsgAtq6dsNe8LUZXfT9gLohsAUEaXz9mJUlloJKzYz2-hD-RD70OBRIOPmELDf90XW-zQp4FigxR47DlNtZ8S9mGYiGMT90Oep0g0BX6UEr-L6Zpjl8KYfbbdwWPYRc8pYZp1fcPTOPUeO95ievANt5nlQx0opsNL9qzFjsKrx_OUXX36eHVxWWy-fv5ycb4pvDYqFbJpK1S2Kg1Kr1AYUdoaK6ulN1LXSppQgSqtNWUjpbWhaVoJoBXWVlpUp-zdYnuNnduPcYfjwQ0Y3eX5xs0z0Dkuq82tyOzZwu7H4ccUKLldzJF13ZKFk9qUWsBaVhl9-w96M0xjnz-SqbVSa2vMTMmF8uNANIb2-AIBbq7WLdW6XK17qNZBFr15tJ7qXWiOkj9dZkAtAOVVvw3j37v_Y_sbpaqwUQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2473379558</pqid></control><display><type>article</type><title>Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Rouault, Christine ; Marcelin, Geneviève ; Adriouch, Solia ; Rose, Cindy ; Genser, Laurent ; Ambrosini, Marc ; Bichet, Jean-Christophe ; Zhang, Yanyan ; Marquet, Florian ; Aron-Wisnewsky, Judith ; Poitou, Christine ; André, Sébastien ; Dérumeaux, Geneviève ; Guerre-Millo, Michèle ; Clément, Karine</creator><creatorcontrib>Rouault, Christine ; Marcelin, Geneviève ; Adriouch, Solia ; Rose, Cindy ; Genser, Laurent ; Ambrosini, Marc ; Bichet, Jean-Christophe ; Zhang, Yanyan ; Marquet, Florian ; Aron-Wisnewsky, Judith ; Poitou, Christine ; André, Sébastien ; Dérumeaux, Geneviève ; Guerre-Millo, Michèle ; Clément, Karine</creatorcontrib><description>Aim/hypothesis
Altered adipose tissue secretory profile contributes to insulin resistance and type 2 diabetes in obesity. Preclinical studies have identified senescent cells as a cellular source of proinflammatory factors in adipose tissue of obese mice. In humans, potential links with obesity comorbidities are poorly defined. Here, we investigated adipose tissue senescent status and relationships with metabolic complications in human obesity.
Methods
The study includes a prospective cohort of 227 individuals with severe obesity. A photometric method was used to quantify senescence-associated β-galactosidase (SA-β-gal) activity in paired subcutaneous and omental adipose tissue biopsies obtained during gastric surgery. Gene and secretory profiling was performed in adipose tissue biopsies and in human primary pre-adipocytes in the presence or absence of senolytic drugs targeting senescent cells. Participants were phenotyped for anthropometric and bioclinical variables, metabolic complications and gastric surgery-induced improvement to address relationships with adipose tissue SA-β-gal.
Results
SA-β-gal activity was sevenfold higher in subcutaneous than in omental adipose tissue and not associated with BMI or chronological age. Several factors, including insulin-like growth factor binding protein 3 (IGFBP3), plasminogen activator inhibitor 1 (PAI1), C–C motif chemokine ligand 2 (CCL2) and IL-6, were upregulated in subcutaneous adipose tissue in relation with SA-β-gal (
p
for linear trend across tertiles <0.05) and in pre-adipocytes cultured with inflammatory macrophage conditioned media. Senolytic treatment reduced SA-β-gal staining and normalised these alterations. In the whole population, subcutaneous adipose tissue SA-β-gal activity was positively associated with serum leptin, markers of insulin resistance and increased trunk fat mass. Metabolic complications, including type 2 diabetes and dyslipidaemia, were more prevalent in patients with high levels of SA-β-gal, but improved with bariatric surgery whatever the initial adipose tissue senescent status.
Conclusions/interpretation
This study highlights a phenotype of senescence in adipose tissue of severely obese individuals, which characterises prominently subcutaneous fat depots. Subcutaneous adipose tissue senescence is significantly linked to altered glucose metabolism and body fat distribution. Elimination of senescent cells through senolytic treatment could alleviate metabolic complications in severely obese people.
Graphical abstract</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-020-05307-0</identifier><identifier>PMID: 33125520</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adipocytes ; Adipocytes - physiology ; Adipose tissue ; Bariatric Surgery ; beta-Galactosidase - metabolism ; Biopsy ; Blood Glucose - analysis ; Body Composition - physiology ; Body fat ; Cellular Senescence - physiology ; Chemokines ; Cohort Studies ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Drug delivery ; Dyslipidemia ; Fat metabolism ; Female ; Gastrointestinal surgery ; Glucose metabolism ; Human Physiology ; Humans ; Inflammation ; Insulin ; Insulin Resistance ; Insulin-like growth factor-binding protein 3 ; Interleukin 6 ; Internal Medicine ; Leptin ; Life Sciences ; Macrophages ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolism ; Monocyte chemoattractant protein 1 ; Obesity ; Obesity, Morbid - metabolism ; Obesity, Morbid - physiopathology ; Obesity, Morbid - surgery ; Phenotypes ; Plasminogen activator inhibitors ; Prospective Studies ; Senescence ; Subcutaneous Fat - enzymology ; Subcutaneous Fat - pathology ; Surgery ; Treatment Outcome ; β-Galactosidase</subject><ispartof>Diabetologia, 2021-01, Vol.64 (1), p.240-254</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020.</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-c453t-2df8a39865a2c3a15169ba8942c524b325e80369956d2299eddf20043ab929a3</citedby><cites>FETCH-LOGICAL-c453t-2df8a39865a2c3a15169ba8942c524b325e80369956d2299eddf20043ab929a3</cites><orcidid>0000-0002-9779-5529 ; 0000-0003-3330-4062 ; 0000-0002-7543-153X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-020-05307-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-020-05307-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33125520$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04000945$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Rouault, Christine</creatorcontrib><creatorcontrib>Marcelin, Geneviève</creatorcontrib><creatorcontrib>Adriouch, Solia</creatorcontrib><creatorcontrib>Rose, Cindy</creatorcontrib><creatorcontrib>Genser, Laurent</creatorcontrib><creatorcontrib>Ambrosini, Marc</creatorcontrib><creatorcontrib>Bichet, Jean-Christophe</creatorcontrib><creatorcontrib>Zhang, Yanyan</creatorcontrib><creatorcontrib>Marquet, Florian</creatorcontrib><creatorcontrib>Aron-Wisnewsky, Judith</creatorcontrib><creatorcontrib>Poitou, Christine</creatorcontrib><creatorcontrib>André, Sébastien</creatorcontrib><creatorcontrib>Dérumeaux, Geneviève</creatorcontrib><creatorcontrib>Guerre-Millo, Michèle</creatorcontrib><creatorcontrib>Clément, Karine</creatorcontrib><title>Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aim/hypothesis
Altered adipose tissue secretory profile contributes to insulin resistance and type 2 diabetes in obesity. Preclinical studies have identified senescent cells as a cellular source of proinflammatory factors in adipose tissue of obese mice. In humans, potential links with obesity comorbidities are poorly defined. Here, we investigated adipose tissue senescent status and relationships with metabolic complications in human obesity.
Methods
The study includes a prospective cohort of 227 individuals with severe obesity. A photometric method was used to quantify senescence-associated β-galactosidase (SA-β-gal) activity in paired subcutaneous and omental adipose tissue biopsies obtained during gastric surgery. Gene and secretory profiling was performed in adipose tissue biopsies and in human primary pre-adipocytes in the presence or absence of senolytic drugs targeting senescent cells. Participants were phenotyped for anthropometric and bioclinical variables, metabolic complications and gastric surgery-induced improvement to address relationships with adipose tissue SA-β-gal.
Results
SA-β-gal activity was sevenfold higher in subcutaneous than in omental adipose tissue and not associated with BMI or chronological age. Several factors, including insulin-like growth factor binding protein 3 (IGFBP3), plasminogen activator inhibitor 1 (PAI1), C–C motif chemokine ligand 2 (CCL2) and IL-6, were upregulated in subcutaneous adipose tissue in relation with SA-β-gal (
p
for linear trend across tertiles <0.05) and in pre-adipocytes cultured with inflammatory macrophage conditioned media. Senolytic treatment reduced SA-β-gal staining and normalised these alterations. In the whole population, subcutaneous adipose tissue SA-β-gal activity was positively associated with serum leptin, markers of insulin resistance and increased trunk fat mass. Metabolic complications, including type 2 diabetes and dyslipidaemia, were more prevalent in patients with high levels of SA-β-gal, but improved with bariatric surgery whatever the initial adipose tissue senescent status.
Conclusions/interpretation
This study highlights a phenotype of senescence in adipose tissue of severely obese individuals, which characterises prominently subcutaneous fat depots. Subcutaneous adipose tissue senescence is significantly linked to altered glucose metabolism and body fat distribution. Elimination of senescent cells through senolytic treatment could alleviate metabolic complications in severely obese people.
Graphical abstract</description><subject>Adipocytes</subject><subject>Adipocytes - physiology</subject><subject>Adipose tissue</subject><subject>Bariatric Surgery</subject><subject>beta-Galactosidase - metabolism</subject><subject>Biopsy</subject><subject>Blood Glucose - analysis</subject><subject>Body Composition - physiology</subject><subject>Body fat</subject><subject>Cellular Senescence - physiology</subject><subject>Chemokines</subject><subject>Cohort Studies</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Drug delivery</subject><subject>Dyslipidemia</subject><subject>Fat metabolism</subject><subject>Female</subject><subject>Gastrointestinal surgery</subject><subject>Glucose metabolism</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Insulin-like growth factor-binding protein 3</subject><subject>Interleukin 6</subject><subject>Internal Medicine</subject><subject>Leptin</subject><subject>Life Sciences</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Metabolism</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Obesity</subject><subject>Obesity, Morbid - metabolism</subject><subject>Obesity, Morbid - physiopathology</subject><subject>Obesity, Morbid - surgery</subject><subject>Phenotypes</subject><subject>Plasminogen activator inhibitors</subject><subject>Prospective Studies</subject><subject>Senescence</subject><subject>Subcutaneous Fat - enzymology</subject><subject>Subcutaneous Fat - pathology</subject><subject>Surgery</subject><subject>Treatment Outcome</subject><subject>β-Galactosidase</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc1u1DAUhS0EokPhBVggS2zKInD9l4mXVQUUaSQWdMHOunGcqatMMuQ6reYteJY-CM-E05RBYsHK0r3fObbPYey1gPcCYP2BAIQ0BUgowChYF_CErYRWsgAtq6dsNe8LUZXfT9gLohsAUEaXz9mJUlloJKzYz2-hD-RD70OBRIOPmELDf90XW-zQp4FigxR47DlNtZ8S9mGYiGMT90Oep0g0BX6UEr-L6Zpjl8KYfbbdwWPYRc8pYZp1fcPTOPUeO95ievANt5nlQx0opsNL9qzFjsKrx_OUXX36eHVxWWy-fv5ycb4pvDYqFbJpK1S2Kg1Kr1AYUdoaK6ulN1LXSppQgSqtNWUjpbWhaVoJoBXWVlpUp-zdYnuNnduPcYfjwQ0Y3eX5xs0z0Dkuq82tyOzZwu7H4ccUKLldzJF13ZKFk9qUWsBaVhl9-w96M0xjnz-SqbVSa2vMTMmF8uNANIb2-AIBbq7WLdW6XK17qNZBFr15tJ7qXWiOkj9dZkAtAOVVvw3j37v_Y_sbpaqwUQ</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Rouault, Christine</creator><creator>Marcelin, Geneviève</creator><creator>Adriouch, Solia</creator><creator>Rose, Cindy</creator><creator>Genser, Laurent</creator><creator>Ambrosini, Marc</creator><creator>Bichet, Jean-Christophe</creator><creator>Zhang, Yanyan</creator><creator>Marquet, Florian</creator><creator>Aron-Wisnewsky, Judith</creator><creator>Poitou, Christine</creator><creator>André, Sébastien</creator><creator>Dérumeaux, Geneviève</creator><creator>Guerre-Millo, Michèle</creator><creator>Clément, Karine</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><general>Springer Verlag</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-9779-5529</orcidid><orcidid>https://orcid.org/0000-0003-3330-4062</orcidid><orcidid>https://orcid.org/0000-0002-7543-153X</orcidid></search><sort><creationdate>20210101</creationdate><title>Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity</title><author>Rouault, Christine ; Marcelin, Geneviève ; Adriouch, Solia ; Rose, Cindy ; Genser, Laurent ; Ambrosini, Marc ; Bichet, Jean-Christophe ; Zhang, Yanyan ; Marquet, Florian ; Aron-Wisnewsky, Judith ; Poitou, Christine ; André, Sébastien ; Dérumeaux, Geneviève ; Guerre-Millo, Michèle ; Clément, Karine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-2df8a39865a2c3a15169ba8942c524b325e80369956d2299eddf20043ab929a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adipocytes</topic><topic>Adipocytes - physiology</topic><topic>Adipose tissue</topic><topic>Bariatric Surgery</topic><topic>beta-Galactosidase - metabolism</topic><topic>Biopsy</topic><topic>Blood Glucose - analysis</topic><topic>Body Composition - physiology</topic><topic>Body fat</topic><topic>Cellular Senescence - physiology</topic><topic>Chemokines</topic><topic>Cohort Studies</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Drug delivery</topic><topic>Dyslipidemia</topic><topic>Fat metabolism</topic><topic>Female</topic><topic>Gastrointestinal surgery</topic><topic>Glucose metabolism</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Insulin-like growth factor-binding protein 3</topic><topic>Interleukin 6</topic><topic>Internal Medicine</topic><topic>Leptin</topic><topic>Life Sciences</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Metabolism</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Obesity</topic><topic>Obesity, Morbid - metabolism</topic><topic>Obesity, Morbid - physiopathology</topic><topic>Obesity, Morbid - surgery</topic><topic>Phenotypes</topic><topic>Plasminogen activator inhibitors</topic><topic>Prospective Studies</topic><topic>Senescence</topic><topic>Subcutaneous Fat - enzymology</topic><topic>Subcutaneous Fat - pathology</topic><topic>Surgery</topic><topic>Treatment Outcome</topic><topic>β-Galactosidase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rouault, Christine</creatorcontrib><creatorcontrib>Marcelin, Geneviève</creatorcontrib><creatorcontrib>Adriouch, Solia</creatorcontrib><creatorcontrib>Rose, Cindy</creatorcontrib><creatorcontrib>Genser, Laurent</creatorcontrib><creatorcontrib>Ambrosini, Marc</creatorcontrib><creatorcontrib>Bichet, Jean-Christophe</creatorcontrib><creatorcontrib>Zhang, Yanyan</creatorcontrib><creatorcontrib>Marquet, Florian</creatorcontrib><creatorcontrib>Aron-Wisnewsky, Judith</creatorcontrib><creatorcontrib>Poitou, Christine</creatorcontrib><creatorcontrib>André, Sébastien</creatorcontrib><creatorcontrib>Dérumeaux, Geneviève</creatorcontrib><creatorcontrib>Guerre-Millo, Michèle</creatorcontrib><creatorcontrib>Clément, Karine</creatorcontrib><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>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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 Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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 China</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rouault, Christine</au><au>Marcelin, Geneviève</au><au>Adriouch, Solia</au><au>Rose, Cindy</au><au>Genser, Laurent</au><au>Ambrosini, Marc</au><au>Bichet, Jean-Christophe</au><au>Zhang, Yanyan</au><au>Marquet, Florian</au><au>Aron-Wisnewsky, Judith</au><au>Poitou, Christine</au><au>André, Sébastien</au><au>Dérumeaux, Geneviève</au><au>Guerre-Millo, Michèle</au><au>Clément, Karine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>64</volume><issue>1</issue><spage>240</spage><epage>254</epage><pages>240-254</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aim/hypothesis
Altered adipose tissue secretory profile contributes to insulin resistance and type 2 diabetes in obesity. Preclinical studies have identified senescent cells as a cellular source of proinflammatory factors in adipose tissue of obese mice. In humans, potential links with obesity comorbidities are poorly defined. Here, we investigated adipose tissue senescent status and relationships with metabolic complications in human obesity.
Methods
The study includes a prospective cohort of 227 individuals with severe obesity. A photometric method was used to quantify senescence-associated β-galactosidase (SA-β-gal) activity in paired subcutaneous and omental adipose tissue biopsies obtained during gastric surgery. Gene and secretory profiling was performed in adipose tissue biopsies and in human primary pre-adipocytes in the presence or absence of senolytic drugs targeting senescent cells. Participants were phenotyped for anthropometric and bioclinical variables, metabolic complications and gastric surgery-induced improvement to address relationships with adipose tissue SA-β-gal.
Results
SA-β-gal activity was sevenfold higher in subcutaneous than in omental adipose tissue and not associated with BMI or chronological age. Several factors, including insulin-like growth factor binding protein 3 (IGFBP3), plasminogen activator inhibitor 1 (PAI1), C–C motif chemokine ligand 2 (CCL2) and IL-6, were upregulated in subcutaneous adipose tissue in relation with SA-β-gal (
p
for linear trend across tertiles <0.05) and in pre-adipocytes cultured with inflammatory macrophage conditioned media. Senolytic treatment reduced SA-β-gal staining and normalised these alterations. In the whole population, subcutaneous adipose tissue SA-β-gal activity was positively associated with serum leptin, markers of insulin resistance and increased trunk fat mass. Metabolic complications, including type 2 diabetes and dyslipidaemia, were more prevalent in patients with high levels of SA-β-gal, but improved with bariatric surgery whatever the initial adipose tissue senescent status.
Conclusions/interpretation
This study highlights a phenotype of senescence in adipose tissue of severely obese individuals, which characterises prominently subcutaneous fat depots. Subcutaneous adipose tissue senescence is significantly linked to altered glucose metabolism and body fat distribution. Elimination of senescent cells through senolytic treatment could alleviate metabolic complications in severely obese people.
Graphical abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>33125520</pmid><doi>10.1007/s00125-020-05307-0</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-9779-5529</orcidid><orcidid>https://orcid.org/0000-0003-3330-4062</orcidid><orcidid>https://orcid.org/0000-0002-7543-153X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-186X |
| ispartof | Diabetologia, 2021-01, Vol.64 (1), p.240-254 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_04000945v1 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adipocytes Adipocytes - physiology Adipose tissue Bariatric Surgery beta-Galactosidase - metabolism Biopsy Blood Glucose - analysis Body Composition - physiology Body fat Cellular Senescence - physiology Chemokines Cohort Studies Diabetes Diabetes mellitus (non-insulin dependent) Drug delivery Dyslipidemia Fat metabolism Female Gastrointestinal surgery Glucose metabolism Human Physiology Humans Inflammation Insulin Insulin Resistance Insulin-like growth factor-binding protein 3 Interleukin 6 Internal Medicine Leptin Life Sciences Macrophages Male Medicine Medicine & Public Health Metabolic Diseases Metabolism Monocyte chemoattractant protein 1 Obesity Obesity, Morbid - metabolism Obesity, Morbid - physiopathology Obesity, Morbid - surgery Phenotypes Plasminogen activator inhibitors Prospective Studies Senescence Subcutaneous Fat - enzymology Subcutaneous Fat - pathology Surgery Treatment Outcome β-Galactosidase |
| title | Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T13%3A31%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Senescence-associated%20%CE%B2-galactosidase%20in%20subcutaneous%20adipose%20tissue%20associates%20with%20altered%20glycaemic%20status%20and%20truncal%20fat%20in%20severe%20obesity&rft.jtitle=Diabetologia&rft.au=Rouault,%20Christine&rft.date=2021-01-01&rft.volume=64&rft.issue=1&rft.spage=240&rft.epage=254&rft.pages=240-254&rft.issn=0012-186X&rft.eissn=1432-0428&rft_id=info:doi/10.1007/s00125-020-05307-0&rft_dat=%3Cproquest_hal_p%3E2456410728%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2473379558&rft_id=info:pmid/33125520&rfr_iscdi=true |