Temporal immmunometabolic profiling of adipose tissue in HFD-induced obesity: manifestations of mast cells in fibrosis and senescence
Background/Objectives: Chronic low-grade inflammation/meta-inflammation in adipose tissue leads to obesity-associated metabolic complications. Despite growing understanding, the roles of immune cell subsets, their interrelationship, and chronological events leading to progression of obesity-associat...
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| Veröffentlicht in: | International Journal of Obesity 2019-06, Vol.43 (6), p.1281-1294 |
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| container_title | International Journal of Obesity |
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| creator | Kumar, Durgesh Pandya, Sanket Kumar Varshney, Salil Shankar, Kripa Rajan, Sujith Srivastava, Ankita Gupta, Abhishek Gupta, Sanchita Vishwakarma, Achchhe Lal Misra, Amit Gaikwad, Anil N. |
| description | Background/Objectives:
Chronic low-grade inflammation/meta-inflammation in adipose tissue leads to obesity-associated metabolic complications. Despite growing understanding, the roles of immune cell subsets, their interrelationship, and chronological events leading to progression of obesity-associated insulin resistance (IR) remains unclear.
Methods:
We carried out temporal immunometabolic profiling of adipose tissue from C57BL/6 mice fed a high-fat diet (HFD) for 4, 8, 12, 16, and 20 weeks. We used clodronate sodium liposomes (CLODs) to deplete macrophages and disodium cromoglycate sodium liposomes (DSCGs) to stabilize mast cells.
Results:
In the temporal HFD settings, mice showed progressive glucose intolerance, insulin resistance, and adipose tissue senescence. Histochemistry analysis of epididymal white adipose tissue (eWAT) using picro-sirius red and Masson’s trichrome staining showed extensive collagen deposition in the 16th and 20th weeks. Flow cytometry analysis of the stromal vascular fraction (SVF) from eWAT revealed T-cell subsets as early-phase components and pro-inflammatory macrophages, as well as mast cells as the later phase components during obesity progression. In our therapeutic strategies, macrophage depletion by CLOD and mast stabilization by DSCG attenuated obesity, adipose tissue fibrosis, and improved whole-body glucose homeostasis. In addition, mast cell stabilization also attenuated senescence (p53 and X-gal staining) in eWAT, signifying the role of mast cells over macrophages during obesity.
Conclusion:
New-generation mast cell stabilizers can be exploited for the treatment of obesity-associated metabolic complications. |
| doi_str_mv | 10.1038/s41366-018-0228-5 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_2235048352</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A587791782</galeid><sourcerecordid>A587791782</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-860b709abe6232eda9a74e3f0e08b98fc87c832ccc04f0edb78a554258a964013</originalsourceid><addsrcrecordid>eNp1kcFu1DAQhiMEotvCA3BBlpC4pYztOHa4VYW2SJW4lLPlOJOtq9heMsmhD8B742ULpRLIB0ue75_x_H9VveFwykGaD9Rw2bY1cFODEKZWz6oNb3Rbq6bTz6sNSNA1qFYdVcdEdwCgFIiX1ZEsFd61elP9uMG4y7ObWIgxrilHXFyfp-DZbs5jmELasjwyN4RdJmRLIFqRhcSuLj7VIQ2rx4HlHiks9x9ZdCmMSItbQk60F0ZHC_M4TbQXjaGfMwViLg2MMCF5TB5fVS9GNxG-frhPqm8Xn2_Or-rrr5dfzs-ua99oWGrTQq-hcz22QgocXOd0g3IEBNN3ZvRGeyOF9x6a8jj02jilGqGM69oGuDyp3h36lt2-r-Wf9i6vcyojrRBSQWOkEo_U1k1oQxrzMjsfA3l7pozWHddmT53-gypnwBh8TljMw6eC938JbtFNyy3laf1l1VOQH0BfvKIZR7ubQ3TzveVg98HbQ_C2BG_3wVtVNG8fNlv7iMMfxe-kCyAOAJVS2uL8uPr_u_4EAmC4Vw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2235048352</pqid></control><display><type>article</type><title>Temporal immmunometabolic profiling of adipose tissue in HFD-induced obesity: manifestations of mast cells in fibrosis and senescence</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature Journals Online</source><creator>Kumar, Durgesh ; Pandya, Sanket Kumar ; Varshney, Salil ; Shankar, Kripa ; Rajan, Sujith ; Srivastava, Ankita ; Gupta, Abhishek ; Gupta, Sanchita ; Vishwakarma, Achchhe Lal ; Misra, Amit ; Gaikwad, Anil N.</creator><creatorcontrib>Kumar, Durgesh ; Pandya, Sanket Kumar ; Varshney, Salil ; Shankar, Kripa ; Rajan, Sujith ; Srivastava, Ankita ; Gupta, Abhishek ; Gupta, Sanchita ; Vishwakarma, Achchhe Lal ; Misra, Amit ; Gaikwad, Anil N.</creatorcontrib><description>Background/Objectives:
Chronic low-grade inflammation/meta-inflammation in adipose tissue leads to obesity-associated metabolic complications. Despite growing understanding, the roles of immune cell subsets, their interrelationship, and chronological events leading to progression of obesity-associated insulin resistance (IR) remains unclear.
Methods:
We carried out temporal immunometabolic profiling of adipose tissue from C57BL/6 mice fed a high-fat diet (HFD) for 4, 8, 12, 16, and 20 weeks. We used clodronate sodium liposomes (CLODs) to deplete macrophages and disodium cromoglycate sodium liposomes (DSCGs) to stabilize mast cells.
Results:
In the temporal HFD settings, mice showed progressive glucose intolerance, insulin resistance, and adipose tissue senescence. Histochemistry analysis of epididymal white adipose tissue (eWAT) using picro-sirius red and Masson’s trichrome staining showed extensive collagen deposition in the 16th and 20th weeks. Flow cytometry analysis of the stromal vascular fraction (SVF) from eWAT revealed T-cell subsets as early-phase components and pro-inflammatory macrophages, as well as mast cells as the later phase components during obesity progression. In our therapeutic strategies, macrophage depletion by CLOD and mast stabilization by DSCG attenuated obesity, adipose tissue fibrosis, and improved whole-body glucose homeostasis. In addition, mast cell stabilization also attenuated senescence (p53 and X-gal staining) in eWAT, signifying the role of mast cells over macrophages during obesity.
Conclusion:
New-generation mast cell stabilizers can be exploited for the treatment of obesity-associated metabolic complications.</description><identifier>ISSN: 0307-0565</identifier><identifier>EISSN: 1476-5497</identifier><identifier>DOI: 10.1038/s41366-018-0228-5</identifier><identifier>PMID: 30301967</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/21 ; 13/31 ; 14/63 ; 38/39 ; 38/77 ; 64/60 ; 692/163/2743/2815 ; 692/163/2743/393 ; 82/1 ; 82/16 ; 82/80 ; Adipose tissue ; Adipose Tissue - immunology ; Adipose Tissue - metabolism ; Adipose Tissue - pathology ; Adipose tissues ; Aging ; Aging - pathology ; Animals ; Bisphosphonates ; Clodronic acid ; Collagen ; Depletion ; Diet, High-Fat ; Disease Models, Animal ; Epidemiology ; Fibrosis ; Fibrosis - pathology ; Flow cytometry ; Glucose ; Glucose tolerance ; Health Promotion and Disease Prevention ; High fat diet ; Histamine ; Histochemistry ; Homeostasis ; Immune system ; Inflammation ; Inflammation - metabolism ; Insulin ; Insulin Resistance ; Internal Medicine ; Intolerance ; Ketogenic diet ; Liposomes ; Lymphocytes T ; Macrophages ; Mast cells ; Mast Cells - pathology ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolism ; Mice ; Mice, Inbred C57BL ; Obesity ; Obesity - immunology ; Obesity - metabolism ; Obesity - pathology ; p53 Protein ; Public Health ; Risk factors ; Senescence ; Sodium ; Stabilization ; Staining</subject><ispartof>International Journal of Obesity, 2019-06, Vol.43 (6), p.1281-1294</ispartof><rights>Springer Nature Limited 2018</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-860b709abe6232eda9a74e3f0e08b98fc87c832ccc04f0edb78a554258a964013</citedby><cites>FETCH-LOGICAL-c470t-860b709abe6232eda9a74e3f0e08b98fc87c832ccc04f0edb78a554258a964013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41366-018-0228-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41366-018-0228-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30301967$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumar, Durgesh</creatorcontrib><creatorcontrib>Pandya, Sanket Kumar</creatorcontrib><creatorcontrib>Varshney, Salil</creatorcontrib><creatorcontrib>Shankar, Kripa</creatorcontrib><creatorcontrib>Rajan, Sujith</creatorcontrib><creatorcontrib>Srivastava, Ankita</creatorcontrib><creatorcontrib>Gupta, Abhishek</creatorcontrib><creatorcontrib>Gupta, Sanchita</creatorcontrib><creatorcontrib>Vishwakarma, Achchhe Lal</creatorcontrib><creatorcontrib>Misra, Amit</creatorcontrib><creatorcontrib>Gaikwad, Anil N.</creatorcontrib><title>Temporal immmunometabolic profiling of adipose tissue in HFD-induced obesity: manifestations of mast cells in fibrosis and senescence</title><title>International Journal of Obesity</title><addtitle>Int J Obes</addtitle><addtitle>Int J Obes (Lond)</addtitle><description>Background/Objectives:
Chronic low-grade inflammation/meta-inflammation in adipose tissue leads to obesity-associated metabolic complications. Despite growing understanding, the roles of immune cell subsets, their interrelationship, and chronological events leading to progression of obesity-associated insulin resistance (IR) remains unclear.
Methods:
We carried out temporal immunometabolic profiling of adipose tissue from C57BL/6 mice fed a high-fat diet (HFD) for 4, 8, 12, 16, and 20 weeks. We used clodronate sodium liposomes (CLODs) to deplete macrophages and disodium cromoglycate sodium liposomes (DSCGs) to stabilize mast cells.
Results:
In the temporal HFD settings, mice showed progressive glucose intolerance, insulin resistance, and adipose tissue senescence. Histochemistry analysis of epididymal white adipose tissue (eWAT) using picro-sirius red and Masson’s trichrome staining showed extensive collagen deposition in the 16th and 20th weeks. Flow cytometry analysis of the stromal vascular fraction (SVF) from eWAT revealed T-cell subsets as early-phase components and pro-inflammatory macrophages, as well as mast cells as the later phase components during obesity progression. In our therapeutic strategies, macrophage depletion by CLOD and mast stabilization by DSCG attenuated obesity, adipose tissue fibrosis, and improved whole-body glucose homeostasis. In addition, mast cell stabilization also attenuated senescence (p53 and X-gal staining) in eWAT, signifying the role of mast cells over macrophages during obesity.
Conclusion:
New-generation mast cell stabilizers can be exploited for the treatment of obesity-associated metabolic complications.</description><subject>13/1</subject><subject>13/21</subject><subject>13/31</subject><subject>14/63</subject><subject>38/39</subject><subject>38/77</subject><subject>64/60</subject><subject>692/163/2743/2815</subject><subject>692/163/2743/393</subject><subject>82/1</subject><subject>82/16</subject><subject>82/80</subject><subject>Adipose tissue</subject><subject>Adipose Tissue - immunology</subject><subject>Adipose Tissue - metabolism</subject><subject>Adipose Tissue - pathology</subject><subject>Adipose tissues</subject><subject>Aging</subject><subject>Aging - pathology</subject><subject>Animals</subject><subject>Bisphosphonates</subject><subject>Clodronic acid</subject><subject>Collagen</subject><subject>Depletion</subject><subject>Diet, High-Fat</subject><subject>Disease Models, Animal</subject><subject>Epidemiology</subject><subject>Fibrosis</subject><subject>Fibrosis - pathology</subject><subject>Flow cytometry</subject><subject>Glucose</subject><subject>Glucose tolerance</subject><subject>Health Promotion and Disease Prevention</subject><subject>High fat diet</subject><subject>Histamine</subject><subject>Histochemistry</subject><subject>Homeostasis</subject><subject>Immune system</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Internal Medicine</subject><subject>Intolerance</subject><subject>Ketogenic diet</subject><subject>Liposomes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Mast cells</subject><subject>Mast Cells - pathology</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Obesity</subject><subject>Obesity - immunology</subject><subject>Obesity - metabolism</subject><subject>Obesity - pathology</subject><subject>p53 Protein</subject><subject>Public Health</subject><subject>Risk factors</subject><subject>Senescence</subject><subject>Sodium</subject><subject>Stabilization</subject><subject>Staining</subject><issn>0307-0565</issn><issn>1476-5497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcFu1DAQhiMEotvCA3BBlpC4pYztOHa4VYW2SJW4lLPlOJOtq9heMsmhD8B742ULpRLIB0ue75_x_H9VveFwykGaD9Rw2bY1cFODEKZWz6oNb3Rbq6bTz6sNSNA1qFYdVcdEdwCgFIiX1ZEsFd61elP9uMG4y7ObWIgxrilHXFyfp-DZbs5jmELasjwyN4RdJmRLIFqRhcSuLj7VIQ2rx4HlHiks9x9ZdCmMSItbQk60F0ZHC_M4TbQXjaGfMwViLg2MMCF5TB5fVS9GNxG-frhPqm8Xn2_Or-rrr5dfzs-ua99oWGrTQq-hcz22QgocXOd0g3IEBNN3ZvRGeyOF9x6a8jj02jilGqGM69oGuDyp3h36lt2-r-Wf9i6vcyojrRBSQWOkEo_U1k1oQxrzMjsfA3l7pozWHddmT53-gypnwBh8TljMw6eC938JbtFNyy3laf1l1VOQH0BfvKIZR7ubQ3TzveVg98HbQ_C2BG_3wVtVNG8fNlv7iMMfxe-kCyAOAJVS2uL8uPr_u_4EAmC4Vw</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Kumar, Durgesh</creator><creator>Pandya, Sanket Kumar</creator><creator>Varshney, Salil</creator><creator>Shankar, Kripa</creator><creator>Rajan, Sujith</creator><creator>Srivastava, Ankita</creator><creator>Gupta, Abhishek</creator><creator>Gupta, Sanchita</creator><creator>Vishwakarma, Achchhe Lal</creator><creator>Misra, Amit</creator><creator>Gaikwad, Anil N.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7T2</scope><scope>7TK</scope><scope>7TS</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8C1</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>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</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>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope></search><sort><creationdate>20190601</creationdate><title>Temporal immmunometabolic profiling of adipose tissue in HFD-induced obesity: manifestations of mast cells in fibrosis and senescence</title><author>Kumar, Durgesh ; Pandya, Sanket Kumar ; Varshney, Salil ; Shankar, Kripa ; Rajan, Sujith ; Srivastava, Ankita ; Gupta, Abhishek ; Gupta, Sanchita ; Vishwakarma, Achchhe Lal ; Misra, Amit ; Gaikwad, Anil N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-860b709abe6232eda9a74e3f0e08b98fc87c832ccc04f0edb78a554258a964013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/1</topic><topic>13/21</topic><topic>13/31</topic><topic>14/63</topic><topic>38/39</topic><topic>38/77</topic><topic>64/60</topic><topic>692/163/2743/2815</topic><topic>692/163/2743/393</topic><topic>82/1</topic><topic>82/16</topic><topic>82/80</topic><topic>Adipose tissue</topic><topic>Adipose Tissue - immunology</topic><topic>Adipose Tissue - metabolism</topic><topic>Adipose Tissue - pathology</topic><topic>Adipose tissues</topic><topic>Aging</topic><topic>Aging - pathology</topic><topic>Animals</topic><topic>Bisphosphonates</topic><topic>Clodronic acid</topic><topic>Collagen</topic><topic>Depletion</topic><topic>Diet, High-Fat</topic><topic>Disease Models, Animal</topic><topic>Epidemiology</topic><topic>Fibrosis</topic><topic>Fibrosis - pathology</topic><topic>Flow cytometry</topic><topic>Glucose</topic><topic>Glucose tolerance</topic><topic>Health Promotion and Disease Prevention</topic><topic>High fat diet</topic><topic>Histamine</topic><topic>Histochemistry</topic><topic>Homeostasis</topic><topic>Immune system</topic><topic>Inflammation</topic><topic>Inflammation - metabolism</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Internal Medicine</topic><topic>Intolerance</topic><topic>Ketogenic diet</topic><topic>Liposomes</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Mast cells</topic><topic>Mast Cells - pathology</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Obesity</topic><topic>Obesity - immunology</topic><topic>Obesity - metabolism</topic><topic>Obesity - pathology</topic><topic>p53 Protein</topic><topic>Public Health</topic><topic>Risk factors</topic><topic>Senescence</topic><topic>Sodium</topic><topic>Stabilization</topic><topic>Staining</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kumar, Durgesh</creatorcontrib><creatorcontrib>Pandya, Sanket Kumar</creatorcontrib><creatorcontrib>Varshney, Salil</creatorcontrib><creatorcontrib>Shankar, Kripa</creatorcontrib><creatorcontrib>Rajan, Sujith</creatorcontrib><creatorcontrib>Srivastava, Ankita</creatorcontrib><creatorcontrib>Gupta, Abhishek</creatorcontrib><creatorcontrib>Gupta, Sanchita</creatorcontrib><creatorcontrib>Vishwakarma, Achchhe Lal</creatorcontrib><creatorcontrib>Misra, Amit</creatorcontrib><creatorcontrib>Gaikwad, Anil N.</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>Health and Safety Science Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</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>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Biological Science 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 One Psychology</collection><collection>ProQuest Central Basic</collection><jtitle>International Journal of Obesity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumar, Durgesh</au><au>Pandya, Sanket Kumar</au><au>Varshney, Salil</au><au>Shankar, Kripa</au><au>Rajan, Sujith</au><au>Srivastava, Ankita</au><au>Gupta, Abhishek</au><au>Gupta, Sanchita</au><au>Vishwakarma, Achchhe Lal</au><au>Misra, Amit</au><au>Gaikwad, Anil N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Temporal immmunometabolic profiling of adipose tissue in HFD-induced obesity: manifestations of mast cells in fibrosis and senescence</atitle><jtitle>International Journal of Obesity</jtitle><stitle>Int J Obes</stitle><addtitle>Int J Obes (Lond)</addtitle><date>2019-06-01</date><risdate>2019</risdate><volume>43</volume><issue>6</issue><spage>1281</spage><epage>1294</epage><pages>1281-1294</pages><issn>0307-0565</issn><eissn>1476-5497</eissn><abstract>Background/Objectives:
Chronic low-grade inflammation/meta-inflammation in adipose tissue leads to obesity-associated metabolic complications. Despite growing understanding, the roles of immune cell subsets, their interrelationship, and chronological events leading to progression of obesity-associated insulin resistance (IR) remains unclear.
Methods:
We carried out temporal immunometabolic profiling of adipose tissue from C57BL/6 mice fed a high-fat diet (HFD) for 4, 8, 12, 16, and 20 weeks. We used clodronate sodium liposomes (CLODs) to deplete macrophages and disodium cromoglycate sodium liposomes (DSCGs) to stabilize mast cells.
Results:
In the temporal HFD settings, mice showed progressive glucose intolerance, insulin resistance, and adipose tissue senescence. Histochemistry analysis of epididymal white adipose tissue (eWAT) using picro-sirius red and Masson’s trichrome staining showed extensive collagen deposition in the 16th and 20th weeks. Flow cytometry analysis of the stromal vascular fraction (SVF) from eWAT revealed T-cell subsets as early-phase components and pro-inflammatory macrophages, as well as mast cells as the later phase components during obesity progression. In our therapeutic strategies, macrophage depletion by CLOD and mast stabilization by DSCG attenuated obesity, adipose tissue fibrosis, and improved whole-body glucose homeostasis. In addition, mast cell stabilization also attenuated senescence (p53 and X-gal staining) in eWAT, signifying the role of mast cells over macrophages during obesity.
Conclusion:
New-generation mast cell stabilizers can be exploited for the treatment of obesity-associated metabolic complications.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30301967</pmid><doi>10.1038/s41366-018-0228-5</doi><tpages>14</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0307-0565 |
| ispartof | International Journal of Obesity, 2019-06, Vol.43 (6), p.1281-1294 |
| issn | 0307-0565 1476-5497 |
| language | eng |
| recordid | cdi_proquest_journals_2235048352 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 13/1 13/21 13/31 14/63 38/39 38/77 64/60 692/163/2743/2815 692/163/2743/393 82/1 82/16 82/80 Adipose tissue Adipose Tissue - immunology Adipose Tissue - metabolism Adipose Tissue - pathology Adipose tissues Aging Aging - pathology Animals Bisphosphonates Clodronic acid Collagen Depletion Diet, High-Fat Disease Models, Animal Epidemiology Fibrosis Fibrosis - pathology Flow cytometry Glucose Glucose tolerance Health Promotion and Disease Prevention High fat diet Histamine Histochemistry Homeostasis Immune system Inflammation Inflammation - metabolism Insulin Insulin Resistance Internal Medicine Intolerance Ketogenic diet Liposomes Lymphocytes T Macrophages Mast cells Mast Cells - pathology Medicine Medicine & Public Health Metabolic Diseases Metabolism Mice Mice, Inbred C57BL Obesity Obesity - immunology Obesity - metabolism Obesity - pathology p53 Protein Public Health Risk factors Senescence Sodium Stabilization Staining |
| title | Temporal immmunometabolic profiling of adipose tissue in HFD-induced obesity: manifestations of mast cells in fibrosis and senescence |
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