Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity
Background: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning...
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| Veröffentlicht in: | Obesity Facts 2020-05, Vol.13 (2), p.130-143 |
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| creator | da Fonseca, Ana Carolina Proença da Fonseca, Guilherme Proença Marchesini, Bruna Voigt, Danielle Dutra Campos Junior, Mario Zembrzuski, Verônica Marques Carneiro, João Regis Ivar Nogueira Neto, José Firmino Cabello, Pedro Hernan Cabello, Giselda Maria Kalil |
| description | Background: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. Objectives:The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5–52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1–23.9]). Methods: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3–5 as well as their intron-exon boundaries was performed using automatic sequencing. Results: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. Conclusion: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity. |
| doi_str_mv | 10.1159/000505666 |
| format | Article |
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During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. Objectives:The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5–52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1–23.9]). Methods: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3–5 as well as their intron-exon boundaries was performed using automatic sequencing. Results: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. Conclusion: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity.</description><identifier>ISSN: 1662-4025</identifier><identifier>EISSN: 1662-4033</identifier><identifier>DOI: 10.1159/000505666</identifier><identifier>PMID: 32325455</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Adipocytes ; Adipose tissue ; Body fat ; Body mass index ; Cholesterol ; Deoxyribonucleic acid ; Diabetes ; DNA ; Endocrinology & Metabolism ; Exercise ; Gastrointestinal surgery ; Gene expression ; Genetic aspects ; Genetic polymorphisms ; Genetic research ; Glucose ; Haplotypes ; Health aspects ; High density lipoprotein ; irisin ; Life Sciences & Biomedicine ; Nutrition & Dietetics ; Obesity ; Overweight ; Physical fitness ; Polymorphism ; ppargc1a ; Proteins ; Research Article ; Risk factors ; Science & Technology ; severe obesity ; ucp1</subject><ispartof>Obesity Facts, 2020-05, Vol.13 (2), p.130-143</ispartof><rights>2020 The Author(s) Published by S. Karger AG, Basel</rights><rights>2020 The Author(s) Published by S. Karger AG, Basel.</rights><rights>COPYRIGHT 2020 S. Karger AG</rights><rights>Copyright © 2020 by S. Karger AG, Basel 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>3</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000533867800003</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c585t-d3e4365d7beadf3a19bb7ecb552497f3d40f10546b46c9e2ab6d31c8325d128e3</citedby><cites>FETCH-LOGICAL-c585t-d3e4365d7beadf3a19bb7ecb552497f3d40f10546b46c9e2ab6d31c8325d128e3</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/PMC7250364/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250364/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2116,27642,27931,27932,28255,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32325455$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>da Fonseca, Ana Carolina Proença </creatorcontrib><creatorcontrib>da Fonseca, Guilherme Proença </creatorcontrib><creatorcontrib>Marchesini, Bruna</creatorcontrib><creatorcontrib>Voigt, Danielle Dutra</creatorcontrib><creatorcontrib>Campos Junior, Mario</creatorcontrib><creatorcontrib>Zembrzuski, Verônica Marques</creatorcontrib><creatorcontrib>Carneiro, João Regis Ivar</creatorcontrib><creatorcontrib>Nogueira Neto, José Firmino</creatorcontrib><creatorcontrib>Cabello, Pedro Hernan</creatorcontrib><creatorcontrib>Cabello, Giselda Maria Kalil</creatorcontrib><title>Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity</title><title>Obesity Facts</title><addtitle>OBESITY FACTS</addtitle><addtitle>Obes Facts</addtitle><description>Background: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. Objectives:The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5–52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1–23.9]). Methods: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3–5 as well as their intron-exon boundaries was performed using automatic sequencing. Results: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. Conclusion: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity.</description><subject>Adipocytes</subject><subject>Adipose tissue</subject><subject>Body fat</subject><subject>Body mass index</subject><subject>Cholesterol</subject><subject>Deoxyribonucleic acid</subject><subject>Diabetes</subject><subject>DNA</subject><subject>Endocrinology & Metabolism</subject><subject>Exercise</subject><subject>Gastrointestinal surgery</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Genetic research</subject><subject>Glucose</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>High density lipoprotein</subject><subject>irisin</subject><subject>Life Sciences & Biomedicine</subject><subject>Nutrition & Dietetics</subject><subject>Obesity</subject><subject>Overweight</subject><subject>Physical fitness</subject><subject>Polymorphism</subject><subject>ppargc1a</subject><subject>Proteins</subject><subject>Research Article</subject><subject>Risk factors</subject><subject>Science & Technology</subject><subject>severe obesity</subject><subject>ucp1</subject><issn>1662-4025</issn><issn>1662-4033</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>M--</sourceid><sourceid>AOWDO</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>DOA</sourceid><recordid>eNqNktuLEzEUxgdR3LX64LvIgC-KdM19Mi9CLe66UKh4ew2ZzJk2vSTdTNrS_960U0dXfJA8JJz8zpfzhS_LnmN0hTEv3yGEOOJCiAfZJRaCDBmi9GF_Jvwie9K2C4QEZgV-nF1QQglnnF9mzQ04iNbkP3Sw2sU2ty6Pc8hHJtqdjta73Denyofg9244sct0WduNN4cI-Wcd53t9yLWrT9AX2y7zxof8K-wgQD6toLXx8DR71OhVC8_O-yD7fv3x2_jTcDK9uR2PJkPDJY_DmgKjgtdFBbpuqMZlVRVgKs4JK4uG1gw1GHEmKiZMCURXoqbYyOSmxkQCHWS3nW7t9UJtgl3rcFBeW3Uq-DBTOiS7K1B1wSuCAEtKGcOMaFRgyYEISiQvK5S03ndam221htqAi0Gv7onev3F2rmZ-pwrCERUsCbw-CwR_t4U2qrVtDaxW2oHftorQkpVIYnlEX_2FLvw2uPRViqThOJMSFYm66qiZTgasa3x616RVw9oa76CxqT4SFEkhGMep4U3XYIJv2wBNPz1G6hgd1UcnsS__tNuTv7KSgLcdsIfKN62x4Az02FGIUikKmU4pfoNM_j89tvEUtbHfuvj7M5Y6zCD0TdPrUTer2qRwDLIX_6TOdn4COwHxxQ</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>da Fonseca, Ana Carolina Proença </creator><creator>da Fonseca, Guilherme Proença </creator><creator>Marchesini, Bruna</creator><creator>Voigt, Danielle Dutra</creator><creator>Campos Junior, Mario</creator><creator>Zembrzuski, Verônica Marques</creator><creator>Carneiro, João Regis Ivar</creator><creator>Nogueira Neto, José Firmino</creator><creator>Cabello, Pedro Hernan</creator><creator>Cabello, Giselda Maria Kalil</creator><general>Karger</general><general>S. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Obesity Facts</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>da Fonseca, Ana Carolina Proença </au><au>da Fonseca, Guilherme Proença </au><au>Marchesini, Bruna</au><au>Voigt, Danielle Dutra</au><au>Campos Junior, Mario</au><au>Zembrzuski, Verônica Marques</au><au>Carneiro, João Regis Ivar</au><au>Nogueira Neto, José Firmino</au><au>Cabello, Pedro Hernan</au><au>Cabello, Giselda Maria Kalil</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity</atitle><jtitle>Obesity Facts</jtitle><stitle>OBESITY FACTS</stitle><addtitle>Obes Facts</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>13</volume><issue>2</issue><spage>130</spage><epage>143</epage><pages>130-143</pages><issn>1662-4025</issn><eissn>1662-4033</eissn><abstract>Background: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. Objectives:The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5–52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1–23.9]). Methods: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3–5 as well as their intron-exon boundaries was performed using automatic sequencing. Results: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. Conclusion: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>32325455</pmid><doi>10.1159/000505666</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Obesity Facts, 2020-05, Vol.13 (2), p.130-143 |
| issn | 1662-4025 1662-4033 |
| language | eng |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Karger Open Access; Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; PubMed Central |
| subjects | Adipocytes Adipose tissue Body fat Body mass index Cholesterol Deoxyribonucleic acid Diabetes DNA Endocrinology & Metabolism Exercise Gastrointestinal surgery Gene expression Genetic aspects Genetic polymorphisms Genetic research Glucose Haplotypes Health aspects High density lipoprotein irisin Life Sciences & Biomedicine Nutrition & Dietetics Obesity Overweight Physical fitness Polymorphism ppargc1a Proteins Research Article Risk factors Science & Technology severe obesity ucp1 |
| title | Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T02%3A31%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_webof&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20Variants%20in%20the%20Activation%20of%20the%20Brown-Like%20Adipocyte%20Pathway%20and%20the%20Risk%20for%20Severe%20Obesity&rft.jtitle=Obesity%20Facts&rft.au=da%C2%A0Fonseca,%20Ana%C2%A0Carolina%C2%A0Proen%C3%A7a%C2%A0&rft.date=2020-05-01&rft.volume=13&rft.issue=2&rft.spage=130&rft.epage=143&rft.pages=130-143&rft.issn=1662-4025&rft.eissn=1662-4033&rft_id=info:doi/10.1159/000505666&rft_dat=%3Cgale_webof%3EA630866451%3C/gale_webof%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2414548807&rft_id=info:pmid/32325455&rft_galeid=A630866451&rft_doaj_id=oai_doaj_org_article_d75b20e183344142a07185e2632859b0&rfr_iscdi=true |