Transferrin receptor levels and its rare variant are associated with human obesity
Aim Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat develop...
Gespeichert in:
| Veröffentlicht in: | Journal of diabetes 2024-01, Vol.16 (1), p.e13467-n/a |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | n/a |
|---|---|
| container_issue | 1 |
| container_start_page | e13467 |
| container_title | Journal of diabetes |
| container_volume | 16 |
| creator | Qiu, Jin Zhang, Zhiyin Hu, Yepeng Guo, Yuhan Liu, Caizhi Chen, Yanru Wang, Dongmei Su, Junlei Wang, Sainan Ni, Mengshan Xu, Sainan Yu, Jian Hu, Tianhui Song, Gaojie Ma, Xinran Gu, Xuejiang Wang, Jiqiu Xu, Lingyan |
| description | Aim
Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown.
Methods
To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon‐sequencing and genetic assessments were conducted of a case–control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole‐exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis.
Results
TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild‐type.
Conclusions
Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.
Highlights
Evidence for contribution of transferrin receptor (Tfrc) and its variants for human thermogenic fat is limited. TFRC levels is elevated in activated human thermogenic fat from pheochromocytoma patients and downregulated in fat from overweight patients compared to their control subjects, respectively.
Whole‐exome sequencing of obese and matched control subjects suggests that a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in young, severely obese subjects.
Structural and functional studies reveal impaired protein stability of the TFRC variant p.I337V compared to wild‐type. |
| doi_str_mv | 10.1111/1753-0407.13467 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10809288</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2858993394</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5507-82dd1fccd2d06a0cc3ea890b5de6578ff50d20d4f5f86ab6dce090c0bd3f3d413</originalsourceid><addsrcrecordid>eNqFkctvVCEUh4nR2Ieu3RkSN26m5XHhwsrYan2kiYmpa8KFg0NzB0a4d5r572WcdqIulA0nnI9fzsmH0AtKzmg757QXfEE60p9R3sn-ETo-vDx-qLnmR-ik1ltCZC8lf4qOeC87SRU7Rl9vik01QCkx4QIO1lMueIQNjBXb5HGcKi62AN7YEm2a8K62tWYX7QQe38VpiZfzyiacB6hx2j5DT4IdKzy_v0_Rt6v3N5cfF9dfPny6fHu9cEKQfqGY9zQ455kn0hLnOFilySA8SNGrEATxjPguiKCkHaR3QDRxZPA8cN9Rfore7HPX87CC1k5TsaNZl7iyZWuyjebPTopL8z1vDCWKaKZUS3h9n1DyjxnqZFaxOhhHmyDP1TAllNac666hr_5Cb_NcUtvP8DaWkrpj-l8U01QzIjrGG3W-p1zJtRYIh5kpMTutZifO7CSaX1rbj5e_r3rgHzw2QOyBuzjC9n955vO7i33wT0Z4rWI</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3090869429</pqid></control><display><type>article</type><title>Transferrin receptor levels and its rare variant are associated with human obesity</title><source>DOAJ Directory of Open Access Journals</source><source>Access via Wiley Online Library</source><source>Wiley Online Library Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Qiu, Jin ; Zhang, Zhiyin ; Hu, Yepeng ; Guo, Yuhan ; Liu, Caizhi ; Chen, Yanru ; Wang, Dongmei ; Su, Junlei ; Wang, Sainan ; Ni, Mengshan ; Xu, Sainan ; Yu, Jian ; Hu, Tianhui ; Song, Gaojie ; Ma, Xinran ; Gu, Xuejiang ; Wang, Jiqiu ; Xu, Lingyan</creator><creatorcontrib>Qiu, Jin ; Zhang, Zhiyin ; Hu, Yepeng ; Guo, Yuhan ; Liu, Caizhi ; Chen, Yanru ; Wang, Dongmei ; Su, Junlei ; Wang, Sainan ; Ni, Mengshan ; Xu, Sainan ; Yu, Jian ; Hu, Tianhui ; Song, Gaojie ; Ma, Xinran ; Gu, Xuejiang ; Wang, Jiqiu ; Xu, Lingyan</creatorcontrib><description>Aim
Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown.
Methods
To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon‐sequencing and genetic assessments were conducted of a case–control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole‐exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis.
Results
TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild‐type.
Conclusions
Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.
Highlights
Evidence for contribution of transferrin receptor (Tfrc) and its variants for human thermogenic fat is limited. TFRC levels is elevated in activated human thermogenic fat from pheochromocytoma patients and downregulated in fat from overweight patients compared to their control subjects, respectively.
Whole‐exome sequencing of obese and matched control subjects suggests that a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in young, severely obese subjects.
Structural and functional studies reveal impaired protein stability of the TFRC variant p.I337V compared to wild‐type.</description><identifier>ISSN: 1753-0393</identifier><identifier>ISSN: 1753-0407</identifier><identifier>EISSN: 1753-0407</identifier><identifier>DOI: 10.1111/1753-0407.13467</identifier><identifier>PMID: 37646182</identifier><language>eng</language><publisher>Melbourne: Wiley Publishing Asia Pty Ltd</publisher><subject>Abdomen ; Adipocytes ; Antibodies ; Biopsy ; Biotechnology ; Body fat ; Body mass index ; brown gene program ; genetic variants ; Homeostasis ; Hospitals ; Metabolic disorders ; Mutation ; Obesity ; Original ; Overweight ; Physiology ; Proteins ; Statistical analysis ; TFRC ; Thermogenesis ; thermogenic adipocytes</subject><ispartof>Journal of diabetes, 2024-01, Vol.16 (1), p.e13467-n/a</ispartof><rights>2023 The Authors. published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.</rights><rights>2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5507-82dd1fccd2d06a0cc3ea890b5de6578ff50d20d4f5f86ab6dce090c0bd3f3d413</citedby><cites>FETCH-LOGICAL-c5507-82dd1fccd2d06a0cc3ea890b5de6578ff50d20d4f5f86ab6dce090c0bd3f3d413</cites><orcidid>0000-0002-8666-5219 ; 0000-0002-7629-7627 ; 0000-0002-9383-7656</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809288/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809288/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37646182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qiu, Jin</creatorcontrib><creatorcontrib>Zhang, Zhiyin</creatorcontrib><creatorcontrib>Hu, Yepeng</creatorcontrib><creatorcontrib>Guo, Yuhan</creatorcontrib><creatorcontrib>Liu, Caizhi</creatorcontrib><creatorcontrib>Chen, Yanru</creatorcontrib><creatorcontrib>Wang, Dongmei</creatorcontrib><creatorcontrib>Su, Junlei</creatorcontrib><creatorcontrib>Wang, Sainan</creatorcontrib><creatorcontrib>Ni, Mengshan</creatorcontrib><creatorcontrib>Xu, Sainan</creatorcontrib><creatorcontrib>Yu, Jian</creatorcontrib><creatorcontrib>Hu, Tianhui</creatorcontrib><creatorcontrib>Song, Gaojie</creatorcontrib><creatorcontrib>Ma, Xinran</creatorcontrib><creatorcontrib>Gu, Xuejiang</creatorcontrib><creatorcontrib>Wang, Jiqiu</creatorcontrib><creatorcontrib>Xu, Lingyan</creatorcontrib><title>Transferrin receptor levels and its rare variant are associated with human obesity</title><title>Journal of diabetes</title><addtitle>J Diabetes</addtitle><description>Aim
Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown.
Methods
To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon‐sequencing and genetic assessments were conducted of a case–control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole‐exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis.
Results
TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild‐type.
Conclusions
Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.
Highlights
Evidence for contribution of transferrin receptor (Tfrc) and its variants for human thermogenic fat is limited. TFRC levels is elevated in activated human thermogenic fat from pheochromocytoma patients and downregulated in fat from overweight patients compared to their control subjects, respectively.
Whole‐exome sequencing of obese and matched control subjects suggests that a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in young, severely obese subjects.
Structural and functional studies reveal impaired protein stability of the TFRC variant p.I337V compared to wild‐type.</description><subject>Abdomen</subject><subject>Adipocytes</subject><subject>Antibodies</subject><subject>Biopsy</subject><subject>Biotechnology</subject><subject>Body fat</subject><subject>Body mass index</subject><subject>brown gene program</subject><subject>genetic variants</subject><subject>Homeostasis</subject><subject>Hospitals</subject><subject>Metabolic disorders</subject><subject>Mutation</subject><subject>Obesity</subject><subject>Original</subject><subject>Overweight</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Statistical analysis</subject><subject>TFRC</subject><subject>Thermogenesis</subject><subject>thermogenic adipocytes</subject><issn>1753-0393</issn><issn>1753-0407</issn><issn>1753-0407</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkctvVCEUh4nR2Ieu3RkSN26m5XHhwsrYan2kiYmpa8KFg0NzB0a4d5r572WcdqIulA0nnI9fzsmH0AtKzmg757QXfEE60p9R3sn-ETo-vDx-qLnmR-ik1ltCZC8lf4qOeC87SRU7Rl9vik01QCkx4QIO1lMueIQNjBXb5HGcKi62AN7YEm2a8K62tWYX7QQe38VpiZfzyiacB6hx2j5DT4IdKzy_v0_Rt6v3N5cfF9dfPny6fHu9cEKQfqGY9zQ455kn0hLnOFilySA8SNGrEATxjPguiKCkHaR3QDRxZPA8cN9Rfore7HPX87CC1k5TsaNZl7iyZWuyjebPTopL8z1vDCWKaKZUS3h9n1DyjxnqZFaxOhhHmyDP1TAllNac666hr_5Cb_NcUtvP8DaWkrpj-l8U01QzIjrGG3W-p1zJtRYIh5kpMTutZifO7CSaX1rbj5e_r3rgHzw2QOyBuzjC9n955vO7i33wT0Z4rWI</recordid><startdate>202401</startdate><enddate>202401</enddate><creator>Qiu, Jin</creator><creator>Zhang, Zhiyin</creator><creator>Hu, Yepeng</creator><creator>Guo, Yuhan</creator><creator>Liu, Caizhi</creator><creator>Chen, Yanru</creator><creator>Wang, Dongmei</creator><creator>Su, Junlei</creator><creator>Wang, Sainan</creator><creator>Ni, Mengshan</creator><creator>Xu, Sainan</creator><creator>Yu, Jian</creator><creator>Hu, Tianhui</creator><creator>Song, Gaojie</creator><creator>Ma, Xinran</creator><creator>Gu, Xuejiang</creator><creator>Wang, Jiqiu</creator><creator>Xu, Lingyan</creator><general>Wiley Publishing Asia Pty Ltd</general><general>John Wiley & Sons, Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</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>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8666-5219</orcidid><orcidid>https://orcid.org/0000-0002-7629-7627</orcidid><orcidid>https://orcid.org/0000-0002-9383-7656</orcidid></search><sort><creationdate>202401</creationdate><title>Transferrin receptor levels and its rare variant are associated with human obesity</title><author>Qiu, Jin ; Zhang, Zhiyin ; Hu, Yepeng ; Guo, Yuhan ; Liu, Caizhi ; Chen, Yanru ; Wang, Dongmei ; Su, Junlei ; Wang, Sainan ; Ni, Mengshan ; Xu, Sainan ; Yu, Jian ; Hu, Tianhui ; Song, Gaojie ; Ma, Xinran ; Gu, Xuejiang ; Wang, Jiqiu ; Xu, Lingyan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5507-82dd1fccd2d06a0cc3ea890b5de6578ff50d20d4f5f86ab6dce090c0bd3f3d413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Abdomen</topic><topic>Adipocytes</topic><topic>Antibodies</topic><topic>Biopsy</topic><topic>Biotechnology</topic><topic>Body fat</topic><topic>Body mass index</topic><topic>brown gene program</topic><topic>genetic variants</topic><topic>Homeostasis</topic><topic>Hospitals</topic><topic>Metabolic disorders</topic><topic>Mutation</topic><topic>Obesity</topic><topic>Original</topic><topic>Overweight</topic><topic>Physiology</topic><topic>Proteins</topic><topic>Statistical analysis</topic><topic>TFRC</topic><topic>Thermogenesis</topic><topic>thermogenic adipocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qiu, Jin</creatorcontrib><creatorcontrib>Zhang, Zhiyin</creatorcontrib><creatorcontrib>Hu, Yepeng</creatorcontrib><creatorcontrib>Guo, Yuhan</creatorcontrib><creatorcontrib>Liu, Caizhi</creatorcontrib><creatorcontrib>Chen, Yanru</creatorcontrib><creatorcontrib>Wang, Dongmei</creatorcontrib><creatorcontrib>Su, Junlei</creatorcontrib><creatorcontrib>Wang, Sainan</creatorcontrib><creatorcontrib>Ni, Mengshan</creatorcontrib><creatorcontrib>Xu, Sainan</creatorcontrib><creatorcontrib>Yu, Jian</creatorcontrib><creatorcontrib>Hu, Tianhui</creatorcontrib><creatorcontrib>Song, Gaojie</creatorcontrib><creatorcontrib>Ma, Xinran</creatorcontrib><creatorcontrib>Gu, Xuejiang</creatorcontrib><creatorcontrib>Wang, Jiqiu</creatorcontrib><creatorcontrib>Xu, Lingyan</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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>Health & Medical Collection (Alumni Edition)</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>PubMed Central (Full Participant titles)</collection><jtitle>Journal of diabetes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qiu, Jin</au><au>Zhang, Zhiyin</au><au>Hu, Yepeng</au><au>Guo, Yuhan</au><au>Liu, Caizhi</au><au>Chen, Yanru</au><au>Wang, Dongmei</au><au>Su, Junlei</au><au>Wang, Sainan</au><au>Ni, Mengshan</au><au>Xu, Sainan</au><au>Yu, Jian</au><au>Hu, Tianhui</au><au>Song, Gaojie</au><au>Ma, Xinran</au><au>Gu, Xuejiang</au><au>Wang, Jiqiu</au><au>Xu, Lingyan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transferrin receptor levels and its rare variant are associated with human obesity</atitle><jtitle>Journal of diabetes</jtitle><addtitle>J Diabetes</addtitle><date>2024-01</date><risdate>2024</risdate><volume>16</volume><issue>1</issue><spage>e13467</spage><epage>n/a</epage><pages>e13467-n/a</pages><issn>1753-0393</issn><issn>1753-0407</issn><eissn>1753-0407</eissn><abstract>Aim
Iron homeostasis is critical for functional respiratory chain complex of mitochondrial, thus potentially contributing to fat biology and energy homeostasis. Transferrin receptor (Tfrc) binds to transferrin for extracellular iron uptake and is recently reported to be involved in brown fat development and functionality. However, whether TFRC levels and variants are associated with human obesity is unknown.
Methods
To investigate the association of TFRC levels and variants with human obesity, fat biopsies were obtained from surgery. Exon‐sequencing and genetic assessments were conducted of a case–control study. For TFRC levels assessment in fat biopsy, 9 overweight and 12 lean subjects were involved. For genetic study, obese (n = 1271) and lean subjects (n = 1455) were involved. TFRC levels were compared in abdominal mesenteric fat of pheochromocytoma patients versus control subjects, and overweight versus lean subjects. For genetic study, whole‐exome sequencing of obese and matched control subjects were conducted and analyzed. In addition, the possible disruption in protein stability of TFRC variant was assessed by structural and molecular analysis.
Results
TFRC levels are increased in human browning adipose tissue and decreased in fat of overweight patients. Besides, TFRC levels are negatively correlated with body mass index and positively correlated with uncoupling protein 1 levels. Furthermore, a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in obese subjects. Structural and functional study reveals impaired protein stability of the TFRC variant compared to wild‐type.
Conclusions
Reduced TFRC levels and its rare variant p.I337V with protein instability are associated with human obesity.
Highlights
Evidence for contribution of transferrin receptor (Tfrc) and its variants for human thermogenic fat is limited. TFRC levels is elevated in activated human thermogenic fat from pheochromocytoma patients and downregulated in fat from overweight patients compared to their control subjects, respectively.
Whole‐exome sequencing of obese and matched control subjects suggests that a rare heterozygous missense variant p.I337V in TFRC shows a tendency to enrich in young, severely obese subjects.
Structural and functional studies reveal impaired protein stability of the TFRC variant p.I337V compared to wild‐type.</abstract><cop>Melbourne</cop><pub>Wiley Publishing Asia Pty Ltd</pub><pmid>37646182</pmid><doi>10.1111/1753-0407.13467</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8666-5219</orcidid><orcidid>https://orcid.org/0000-0002-7629-7627</orcidid><orcidid>https://orcid.org/0000-0002-9383-7656</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1753-0393 |
| ispartof | Journal of diabetes, 2024-01, Vol.16 (1), p.e13467-n/a |
| issn | 1753-0393 1753-0407 1753-0407 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10809288 |
| source | DOAJ Directory of Open Access Journals; Access via Wiley Online Library; Wiley Online Library Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Abdomen Adipocytes Antibodies Biopsy Biotechnology Body fat Body mass index brown gene program genetic variants Homeostasis Hospitals Metabolic disorders Mutation Obesity Original Overweight Physiology Proteins Statistical analysis TFRC Thermogenesis thermogenic adipocytes |
| title | Transferrin receptor levels and its rare variant are associated with human obesity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T17%3A11%3A38IST&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=Transferrin%20receptor%20levels%20and%20its%20rare%20variant%20are%20associated%20with%20human%20obesity&rft.jtitle=Journal%20of%20diabetes&rft.au=Qiu,%20Jin&rft.date=2024-01&rft.volume=16&rft.issue=1&rft.spage=e13467&rft.epage=n/a&rft.pages=e13467-n/a&rft.issn=1753-0393&rft.eissn=1753-0407&rft_id=info:doi/10.1111/1753-0407.13467&rft_dat=%3Cproquest_pubme%3E2858993394%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3090869429&rft_id=info:pmid/37646182&rfr_iscdi=true |