Loading…
Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes
Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an o...
Saved in:
Published in: | The Journal of clinical investigation 1998-10, Vol.102 (7), p.1345-1351 |
---|---|
Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c467t-4ea9c94fc7fea827bab204ed876ce4e13813a3527da452ebd7a086c06cedc3e83 |
---|---|
cites | |
container_end_page | 1351 |
container_issue | 7 |
container_start_page | 1345 |
container_title | The Journal of clinical investigation |
container_volume | 102 |
creator | Argyropoulos, G Brown, A M Willi, S M Zhu, J He, Y Reitman, M Gevao, S M Spruill, I Garvey, W T |
description | Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning. |
doi_str_mv | 10.1172/jci4115 |
format | article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_508981</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69957051</sourcerecordid><originalsourceid>FETCH-LOGICAL-c467t-4ea9c94fc7fea827bab204ed876ce4e13813a3527da452ebd7a086c06cedc3e83</originalsourceid><addsrcrecordid>eNpVkc1u2zAQhHlIkR8nyBME4Kk9OSVFSpQOPRRGflwY6CU5EytqZTOQSIWkjPop-sqVY8NITwvsfDs7wBByy9k95yr7_mas5Dw_I5eMZXxeKVFekKsY3xjjUubynJxXqqhEVlySvw9tiyZF6lvajwmS9S5S62jaIN2MPTg6OuPHobNuTYfgE06ioGt0SP0BCxgHGyD5sKPvo08WXaLgGtpCov6PbT5c96YRtximuxqjTbsPJu0GpBltLNSYMF6TLy10EW-Oc0ZeHx9eFs_z1e-n5eLnam5kodJcIlSmkq1RLUKZqRrqjElsSlUYlMhFyQWIPFMNyDzDulHAysKwSW2MwFLMyI-D7zDW_bSbIgfo9BBsD2GnPVj9v-LsRq_9VuesrCbzGfl6vA_-fcSYdG-jwa4Dh36MuqiqXLF8D347gCb4GAO2px-c6X1d-tdiua9rIu8-Rzpxx67EPymrltA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69957051</pqid></control><display><type>article</type><title>Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes</title><source>PubMed Central</source><source>EZB Electronic Journals Library</source><creator>Argyropoulos, G ; Brown, A M ; Willi, S M ; Zhu, J ; He, Y ; Reitman, M ; Gevao, S M ; Spruill, I ; Garvey, W T</creator><creatorcontrib>Argyropoulos, G ; Brown, A M ; Willi, S M ; Zhu, J ; He, Y ; Reitman, M ; Gevao, S M ; Spruill, I ; Garvey, W T</creatorcontrib><description>Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning.</description><identifier>ISSN: 0021-9738</identifier><identifier>DOI: 10.1172/jci4115</identifier><identifier>PMID: 9769326</identifier><language>eng</language><publisher>United States</publisher><subject>Alternative Splicing ; Base Sequence ; Black or African American ; Black People - genetics ; Carrier Proteins - chemistry ; Carrier Proteins - genetics ; Codon, Terminator ; Diabetes Mellitus - genetics ; Diabetes Mellitus - metabolism ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Energy Metabolism - genetics ; Ethnicity ; Exons ; Female ; Genetic Carrier Screening ; Humans ; Ion Channels ; Lipolysis - genetics ; Male ; Mitochondrial Proteins ; Models, Molecular ; Obesity ; Oxygen Consumption - genetics ; Pedigree ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Protein Conformation ; Sierra Leone ; Uncoupling Protein 3 ; White People - genetics</subject><ispartof>The Journal of clinical investigation, 1998-10, Vol.102 (7), p.1345-1351</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-4ea9c94fc7fea827bab204ed876ce4e13813a3527da452ebd7a086c06cedc3e83</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC508981/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC508981/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9769326$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Argyropoulos, G</creatorcontrib><creatorcontrib>Brown, A M</creatorcontrib><creatorcontrib>Willi, S M</creatorcontrib><creatorcontrib>Zhu, J</creatorcontrib><creatorcontrib>He, Y</creatorcontrib><creatorcontrib>Reitman, M</creatorcontrib><creatorcontrib>Gevao, S M</creatorcontrib><creatorcontrib>Spruill, I</creatorcontrib><creatorcontrib>Garvey, W T</creatorcontrib><title>Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning.</description><subject>Alternative Splicing</subject><subject>Base Sequence</subject><subject>Black or African American</subject><subject>Black People - genetics</subject><subject>Carrier Proteins - chemistry</subject><subject>Carrier Proteins - genetics</subject><subject>Codon, Terminator</subject><subject>Diabetes Mellitus - genetics</subject><subject>Diabetes Mellitus - metabolism</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Energy Metabolism - genetics</subject><subject>Ethnicity</subject><subject>Exons</subject><subject>Female</subject><subject>Genetic Carrier Screening</subject><subject>Humans</subject><subject>Ion Channels</subject><subject>Lipolysis - genetics</subject><subject>Male</subject><subject>Mitochondrial Proteins</subject><subject>Models, Molecular</subject><subject>Obesity</subject><subject>Oxygen Consumption - genetics</subject><subject>Pedigree</subject><subject>Point Mutation</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic</subject><subject>Protein Conformation</subject><subject>Sierra Leone</subject><subject>Uncoupling Protein 3</subject><subject>White People - genetics</subject><issn>0021-9738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><recordid>eNpVkc1u2zAQhHlIkR8nyBME4Kk9OSVFSpQOPRRGflwY6CU5EytqZTOQSIWkjPop-sqVY8NITwvsfDs7wBByy9k95yr7_mas5Dw_I5eMZXxeKVFekKsY3xjjUubynJxXqqhEVlySvw9tiyZF6lvajwmS9S5S62jaIN2MPTg6OuPHobNuTYfgE06ioGt0SP0BCxgHGyD5sKPvo08WXaLgGtpCov6PbT5c96YRtximuxqjTbsPJu0GpBltLNSYMF6TLy10EW-Oc0ZeHx9eFs_z1e-n5eLnam5kodJcIlSmkq1RLUKZqRrqjElsSlUYlMhFyQWIPFMNyDzDulHAysKwSW2MwFLMyI-D7zDW_bSbIgfo9BBsD2GnPVj9v-LsRq_9VuesrCbzGfl6vA_-fcSYdG-jwa4Dh36MuqiqXLF8D347gCb4GAO2px-c6X1d-tdiua9rIu8-Rzpxx67EPymrltA</recordid><startdate>19981001</startdate><enddate>19981001</enddate><creator>Argyropoulos, G</creator><creator>Brown, A M</creator><creator>Willi, S M</creator><creator>Zhu, J</creator><creator>He, Y</creator><creator>Reitman, M</creator><creator>Gevao, S M</creator><creator>Spruill, I</creator><creator>Garvey, W T</creator><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>19981001</creationdate><title>Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes</title><author>Argyropoulos, G ; Brown, A M ; Willi, S M ; Zhu, J ; He, Y ; Reitman, M ; Gevao, S M ; Spruill, I ; Garvey, W T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-4ea9c94fc7fea827bab204ed876ce4e13813a3527da452ebd7a086c06cedc3e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Alternative Splicing</topic><topic>Base Sequence</topic><topic>Black or African American</topic><topic>Black People - genetics</topic><topic>Carrier Proteins - chemistry</topic><topic>Carrier Proteins - genetics</topic><topic>Codon, Terminator</topic><topic>Diabetes Mellitus - genetics</topic><topic>Diabetes Mellitus - metabolism</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Energy Metabolism - genetics</topic><topic>Ethnicity</topic><topic>Exons</topic><topic>Female</topic><topic>Genetic Carrier Screening</topic><topic>Humans</topic><topic>Ion Channels</topic><topic>Lipolysis - genetics</topic><topic>Male</topic><topic>Mitochondrial Proteins</topic><topic>Models, Molecular</topic><topic>Obesity</topic><topic>Oxygen Consumption - genetics</topic><topic>Pedigree</topic><topic>Point Mutation</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic</topic><topic>Protein Conformation</topic><topic>Sierra Leone</topic><topic>Uncoupling Protein 3</topic><topic>White People - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Argyropoulos, G</creatorcontrib><creatorcontrib>Brown, A M</creatorcontrib><creatorcontrib>Willi, S M</creatorcontrib><creatorcontrib>Zhu, J</creatorcontrib><creatorcontrib>He, Y</creatorcontrib><creatorcontrib>Reitman, M</creatorcontrib><creatorcontrib>Gevao, S M</creatorcontrib><creatorcontrib>Spruill, I</creatorcontrib><creatorcontrib>Garvey, W T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Argyropoulos, G</au><au>Brown, A M</au><au>Willi, S M</au><au>Zhu, J</au><au>He, Y</au><au>Reitman, M</au><au>Gevao, S M</au><au>Spruill, I</au><au>Garvey, W T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>1998-10-01</date><risdate>1998</risdate><volume>102</volume><issue>7</issue><spage>1345</spage><epage>1351</epage><pages>1345-1351</pages><issn>0021-9738</issn><abstract>Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning.</abstract><cop>United States</cop><pmid>9769326</pmid><doi>10.1172/jci4115</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0021-9738 |
ispartof | The Journal of clinical investigation, 1998-10, Vol.102 (7), p.1345-1351 |
issn | 0021-9738 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_508981 |
source | PubMed Central; EZB Electronic Journals Library |
subjects | Alternative Splicing Base Sequence Black or African American Black People - genetics Carrier Proteins - chemistry Carrier Proteins - genetics Codon, Terminator Diabetes Mellitus - genetics Diabetes Mellitus - metabolism Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Energy Metabolism - genetics Ethnicity Exons Female Genetic Carrier Screening Humans Ion Channels Lipolysis - genetics Male Mitochondrial Proteins Models, Molecular Obesity Oxygen Consumption - genetics Pedigree Point Mutation Polymerase Chain Reaction Polymorphism, Genetic Protein Conformation Sierra Leone Uncoupling Protein 3 White People - genetics |
title | Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T15%3A53%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effects%20of%20mutations%20in%20the%20human%20uncoupling%20protein%203%20gene%20on%20the%20respiratory%20quotient%20and%20fat%20oxidation%20in%20severe%20obesity%20and%20type%202%20diabetes&rft.jtitle=The%20Journal%20of%20clinical%20investigation&rft.au=Argyropoulos,%20G&rft.date=1998-10-01&rft.volume=102&rft.issue=7&rft.spage=1345&rft.epage=1351&rft.pages=1345-1351&rft.issn=0021-9738&rft_id=info:doi/10.1172/jci4115&rft_dat=%3Cproquest_pubme%3E69957051%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c467t-4ea9c94fc7fea827bab204ed876ce4e13813a3527da452ebd7a086c06cedc3e83%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=69957051&rft_id=info:pmid/9769326&rfr_iscdi=true |