Whole Blood RNA as a Source of Transcript-Based Nutrition- and Metabolic Health-Related Biomarkers
Blood cells are receiving an increasing attention as an easily accessible source of transcript-based biomarkers. We studied the feasibility of using mouse whole blood RNA in this context. Several paradigms were studied: (i) metabolism-related transcripts known to be affected in rat tissues and perip...
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| Veröffentlicht in: | PloS one 2016-05, Vol.11 (5), p.e0155361-e0155361 |
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| creator | Petrov, Petar D Bonet, M Luisa Reynés, Bárbara Oliver, Paula Palou, Andreu Ribot, Joan |
| description | Blood cells are receiving an increasing attention as an easily accessible source of transcript-based biomarkers. We studied the feasibility of using mouse whole blood RNA in this context. Several paradigms were studied: (i) metabolism-related transcripts known to be affected in rat tissues and peripheral blood mononuclear cells (PBMC) by fasting and upon the development of high fat diet (HFD)-induced overweight were assessed in whole blood RNA of fasted rats and mice and of HFD-fed mice; (ii) retinoic acid (RA)-responsive genes in tissues were assessed in whole blood RNA of control and RA-treated mice; (iii) lipid metabolism-related transcripts previously identified in PBMC as potential biomarkers of metabolic health in a rat model were assessed in whole blood in an independent model, namely retinoblastoma haploinsufficient (Rb+/-) mice. Blood was collected and stored in RNAlater® at -80°C until analysis of selected transcripts by real-time RT-PCR. Comparable changes with fasting were detected in the expression of lipid metabolism-related genes when RNA from either PBMC or whole blood of rats or mice was used. HFD-induced excess body weight and fat mass associated with expected changes in the expression of metabolism-related genes in whole blood of mice. Changes in gene expression in whole blood of RA-treated mice reproduced known transcriptional actions of RA in hepatocytes and adipocytes. Reduced expression of Fasn, Lrp1, Rxrb and Sorl1 could be validated as early biomarkers of metabolic health in young Rb+/- mice using whole blood RNA. Altogether, these results support the use of whole blood RNA in studies aimed at identifying blood transcript-based biomarkers of nutritional/metabolic status or metabolic health. Results also support reduced expression of Fasn, Lrp1, Rxrb and Sorl1 in blood cells at young age as potential biomarkers of metabolic robustness. |
| doi_str_mv | 10.1371/journal.pone.0155361 |
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We studied the feasibility of using mouse whole blood RNA in this context. Several paradigms were studied: (i) metabolism-related transcripts known to be affected in rat tissues and peripheral blood mononuclear cells (PBMC) by fasting and upon the development of high fat diet (HFD)-induced overweight were assessed in whole blood RNA of fasted rats and mice and of HFD-fed mice; (ii) retinoic acid (RA)-responsive genes in tissues were assessed in whole blood RNA of control and RA-treated mice; (iii) lipid metabolism-related transcripts previously identified in PBMC as potential biomarkers of metabolic health in a rat model were assessed in whole blood in an independent model, namely retinoblastoma haploinsufficient (Rb+/-) mice. Blood was collected and stored in RNAlater® at -80°C until analysis of selected transcripts by real-time RT-PCR. Comparable changes with fasting were detected in the expression of lipid metabolism-related genes when RNA from either PBMC or whole blood of rats or mice was used. HFD-induced excess body weight and fat mass associated with expected changes in the expression of metabolism-related genes in whole blood of mice. Changes in gene expression in whole blood of RA-treated mice reproduced known transcriptional actions of RA in hepatocytes and adipocytes. Reduced expression of Fasn, Lrp1, Rxrb and Sorl1 could be validated as early biomarkers of metabolic health in young Rb+/- mice using whole blood RNA. Altogether, these results support the use of whole blood RNA in studies aimed at identifying blood transcript-based biomarkers of nutritional/metabolic status or metabolic health. Results also support reduced expression of Fasn, Lrp1, Rxrb and Sorl1 in blood cells at young age as potential biomarkers of metabolic robustness.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0155361</identifier><identifier>PMID: 27163124</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adipocytes ; Adipocytes - cytology ; Adipocytes - drug effects ; Adipocytes - metabolism ; Analysis ; Animal tissues ; Animals ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Biotechnology ; Blood ; Blood cells ; Body fat ; Body weight ; Body Weight - drug effects ; Cancer ; Diet ; Diet, High-Fat ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Energy Metabolism - drug effects ; Energy Metabolism - genetics ; Fasting ; Fatty Acid Synthase, Type I - genetics ; Fatty Acid Synthase, Type I - metabolism ; Feasibility studies ; Female ; Gene expression ; Gene Expression Regulation ; Genes ; Haploinsufficiency ; Health ; Hepatocytes ; Hepatocytes - cytology ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; High fat diet ; Laboratory animals ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - cytology ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - metabolism ; Lipid metabolism ; Lipids ; Male ; Medicine and Health Sciences ; Membrane Transport Proteins - genetics ; Membrane Transport Proteins - metabolism ; Metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular biology ; Nutrition ; Nutritional Status - drug effects ; Nutritional Status - genetics ; Obesity ; Overweight ; Oxidation ; Peripheral blood mononuclear cells ; Physiology ; Polymerase chain reaction ; Proteins ; Rats ; Rats, Wistar ; Receptors, LDL - genetics ; Receptors, LDL - metabolism ; Research and Analysis Methods ; Retina ; Retinoblastoma ; Retinoblastoma Protein - deficiency ; Retinoblastoma Protein - genetics ; Retinoic acid ; Ribonucleic acid ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Rubidium ; Studies ; Transcription ; Transcriptome ; Tretinoin - administration & dosage ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Vitamin A</subject><ispartof>PloS one, 2016-05, Vol.11 (5), p.e0155361-e0155361</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Petrov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Petrov et al 2016 Petrov et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-21569adee206980908719b54d29baa7d4af708f850a28ea71d2d1f557a115c203</citedby><cites>FETCH-LOGICAL-c725t-21569adee206980908719b54d29baa7d4af708f850a28ea71d2d1f557a115c203</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/PMC4862680/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862680/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27163124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Rajasingh, Johnson</contributor><creatorcontrib>Petrov, Petar D</creatorcontrib><creatorcontrib>Bonet, M Luisa</creatorcontrib><creatorcontrib>Reynés, Bárbara</creatorcontrib><creatorcontrib>Oliver, Paula</creatorcontrib><creatorcontrib>Palou, Andreu</creatorcontrib><creatorcontrib>Ribot, Joan</creatorcontrib><title>Whole Blood RNA as a Source of Transcript-Based Nutrition- and Metabolic Health-Related Biomarkers</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Blood cells are receiving an increasing attention as an easily accessible source of transcript-based biomarkers. We studied the feasibility of using mouse whole blood RNA in this context. Several paradigms were studied: (i) metabolism-related transcripts known to be affected in rat tissues and peripheral blood mononuclear cells (PBMC) by fasting and upon the development of high fat diet (HFD)-induced overweight were assessed in whole blood RNA of fasted rats and mice and of HFD-fed mice; (ii) retinoic acid (RA)-responsive genes in tissues were assessed in whole blood RNA of control and RA-treated mice; (iii) lipid metabolism-related transcripts previously identified in PBMC as potential biomarkers of metabolic health in a rat model were assessed in whole blood in an independent model, namely retinoblastoma haploinsufficient (Rb+/-) mice. Blood was collected and stored in RNAlater® at -80°C until analysis of selected transcripts by real-time RT-PCR. Comparable changes with fasting were detected in the expression of lipid metabolism-related genes when RNA from either PBMC or whole blood of rats or mice was used. HFD-induced excess body weight and fat mass associated with expected changes in the expression of metabolism-related genes in whole blood of mice. Changes in gene expression in whole blood of RA-treated mice reproduced known transcriptional actions of RA in hepatocytes and adipocytes. Reduced expression of Fasn, Lrp1, Rxrb and Sorl1 could be validated as early biomarkers of metabolic health in young Rb+/- mice using whole blood RNA. Altogether, these results support the use of whole blood RNA in studies aimed at identifying blood transcript-based biomarkers of nutritional/metabolic status or metabolic health. Results also support reduced expression of Fasn, Lrp1, Rxrb and Sorl1 in blood cells at young age as potential biomarkers of metabolic robustness.</description><subject>Adipocytes</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - metabolism</subject><subject>Analysis</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biotechnology</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Body fat</subject><subject>Body weight</subject><subject>Body Weight - drug effects</subject><subject>Cancer</subject><subject>Diet</subject><subject>Diet, High-Fat</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Energy Metabolism - drug effects</subject><subject>Energy Metabolism - genetics</subject><subject>Fasting</subject><subject>Fatty Acid Synthase, Type I - genetics</subject><subject>Fatty Acid Synthase, Type I - metabolism</subject><subject>Feasibility studies</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Haploinsufficiency</subject><subject>Health</subject><subject>Hepatocytes</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>High fat diet</subject><subject>Laboratory animals</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - cytology</subject><subject>Leukocytes, Mononuclear - drug effects</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Membrane Transport Proteins - genetics</subject><subject>Membrane Transport Proteins - metabolism</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Molecular biology</subject><subject>Nutrition</subject><subject>Nutritional Status - drug effects</subject><subject>Nutritional Status - genetics</subject><subject>Obesity</subject><subject>Overweight</subject><subject>Oxidation</subject><subject>Peripheral blood mononuclear cells</subject><subject>Physiology</subject><subject>Polymerase chain reaction</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, LDL - genetics</subject><subject>Receptors, LDL - metabolism</subject><subject>Research and Analysis Methods</subject><subject>Retina</subject><subject>Retinoblastoma</subject><subject>Retinoblastoma Protein - deficiency</subject><subject>Retinoblastoma Protein - genetics</subject><subject>Retinoic acid</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Rubidium</subject><subject>Studies</subject><subject>Transcription</subject><subject>Transcriptome</subject><subject>Tretinoin - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content 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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petrov, Petar D</au><au>Bonet, M Luisa</au><au>Reynés, Bárbara</au><au>Oliver, Paula</au><au>Palou, Andreu</au><au>Ribot, Joan</au><au>Rajasingh, Johnson</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Whole Blood RNA as a Source of Transcript-Based Nutrition- and Metabolic Health-Related Biomarkers</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-05-10</date><risdate>2016</risdate><volume>11</volume><issue>5</issue><spage>e0155361</spage><epage>e0155361</epage><pages>e0155361-e0155361</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Blood cells are receiving an increasing attention as an easily accessible source of transcript-based biomarkers. We studied the feasibility of using mouse whole blood RNA in this context. Several paradigms were studied: (i) metabolism-related transcripts known to be affected in rat tissues and peripheral blood mononuclear cells (PBMC) by fasting and upon the development of high fat diet (HFD)-induced overweight were assessed in whole blood RNA of fasted rats and mice and of HFD-fed mice; (ii) retinoic acid (RA)-responsive genes in tissues were assessed in whole blood RNA of control and RA-treated mice; (iii) lipid metabolism-related transcripts previously identified in PBMC as potential biomarkers of metabolic health in a rat model were assessed in whole blood in an independent model, namely retinoblastoma haploinsufficient (Rb+/-) mice. Blood was collected and stored in RNAlater® at -80°C until analysis of selected transcripts by real-time RT-PCR. Comparable changes with fasting were detected in the expression of lipid metabolism-related genes when RNA from either PBMC or whole blood of rats or mice was used. HFD-induced excess body weight and fat mass associated with expected changes in the expression of metabolism-related genes in whole blood of mice. Changes in gene expression in whole blood of RA-treated mice reproduced known transcriptional actions of RA in hepatocytes and adipocytes. Reduced expression of Fasn, Lrp1, Rxrb and Sorl1 could be validated as early biomarkers of metabolic health in young Rb+/- mice using whole blood RNA. Altogether, these results support the use of whole blood RNA in studies aimed at identifying blood transcript-based biomarkers of nutritional/metabolic status or metabolic health. Results also support reduced expression of Fasn, Lrp1, Rxrb and Sorl1 in blood cells at young age as potential biomarkers of metabolic robustness.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27163124</pmid><doi>10.1371/journal.pone.0155361</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-05, Vol.11 (5), p.e0155361-e0155361 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1787932220 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adipocytes Adipocytes - cytology Adipocytes - drug effects Adipocytes - metabolism Analysis Animal tissues Animals Biological markers Biology and Life Sciences Biomarkers Biotechnology Blood Blood cells Body fat Body weight Body Weight - drug effects Cancer Diet Diet, High-Fat DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Energy Metabolism - drug effects Energy Metabolism - genetics Fasting Fatty Acid Synthase, Type I - genetics Fatty Acid Synthase, Type I - metabolism Feasibility studies Female Gene expression Gene Expression Regulation Genes Haploinsufficiency Health Hepatocytes Hepatocytes - cytology Hepatocytes - drug effects Hepatocytes - metabolism High fat diet Laboratory animals Leukocytes (mononuclear) Leukocytes, Mononuclear - cytology Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - metabolism Lipid metabolism Lipids Male Medicine and Health Sciences Membrane Transport Proteins - genetics Membrane Transport Proteins - metabolism Metabolism Mice Mice, Inbred C57BL Mice, Transgenic Molecular biology Nutrition Nutritional Status - drug effects Nutritional Status - genetics Obesity Overweight Oxidation Peripheral blood mononuclear cells Physiology Polymerase chain reaction Proteins Rats Rats, Wistar Receptors, LDL - genetics Receptors, LDL - metabolism Research and Analysis Methods Retina Retinoblastoma Retinoblastoma Protein - deficiency Retinoblastoma Protein - genetics Retinoic acid Ribonucleic acid RNA RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Rubidium Studies Transcription Transcriptome Tretinoin - administration & dosage Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Vitamin A |
| title | Whole Blood RNA as a Source of Transcript-Based Nutrition- and Metabolic Health-Related Biomarkers |
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