Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats
Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites bef...
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creator | Regnell, Simon E Hessner, Martin J Jia, Shuang Åkesson, Lina Stenlund, Hans Moritz, Thomas La Torre, Daria Lernmark, Åke |
description | Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes. |
doi_str_mv | 10.1371/journal.pone.0171372 |
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It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0171372</identifier><identifier>PMID: 28192442</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Annotations ; Biology and Life Sciences ; Blood Glucose - metabolism ; Breeding ; Carbohydrates ; Care and treatment ; Celiac disease ; Cell and Molecular Biology ; Cell- och molekylärbiologi ; Children & youth ; Clinical Medicine ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (insulin dependent) ; Diabetes Mellitus, Type 1 - blood ; Diabetes Mellitus, Type 1 - genetics ; Diabetes Mellitus, Type 1 - metabolism ; Endocrinology and Diabetes ; Endokrinologi och diabetes ; Fat metabolism ; Fatty acids ; Female ; Gas Chromatography-Mass Spectrometry ; Gene expression ; Gene Expression Profiling - methods ; Hospitals ; Hyperglycemia ; Hyperglycemia - blood ; Hyperglycemia - genetics ; Hyperglycemia - metabolism ; Hypotheses ; Insulin ; Insulin - metabolism ; Klinisk medicin ; Laboratory animals ; Lipid metabolism ; Lipid Metabolism - genetics ; Lipids ; Liver ; Liver - metabolism ; Male ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicine and Health Sciences ; Metabolism ; Metabolites ; Metabolome ; Metabolomics - methods ; NMR ; Nuclear magnetic resonance ; Pancreatic beta cells ; Physical Sciences ; Physiological aspects ; Rats ; Rats, Inbred BB ; Rats, Inbred F344 ; Rodents ; Signal Transduction - genetics ; Time Factors ; Transcriptome - genetics ; Urine</subject><ispartof>PloS one, 2017-02, Vol.12 (2), p.e0171372-e0171372</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Regnell 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>2017 Regnell et al 2017 Regnell et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c870t-7fef5adecd25ee607ab141484d95fd617dcdcd0987ff98f12ec95ce800c262d83</citedby><cites>FETCH-LOGICAL-c870t-7fef5adecd25ee607ab141484d95fd617dcdcd0987ff98f12ec95ce800c262d83</cites><orcidid>0000-0002-6672-8972</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/PMC5305198/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5305198/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,552,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28192442$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-132960$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/b4856ec4-7fb5-4ba4-99e3-746dd465f3fe$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://res.slu.se/id/publ/86422$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Peterson, Jonathan M</contributor><creatorcontrib>Regnell, Simon E</creatorcontrib><creatorcontrib>Hessner, Martin J</creatorcontrib><creatorcontrib>Jia, Shuang</creatorcontrib><creatorcontrib>Åkesson, Lina</creatorcontrib><creatorcontrib>Stenlund, Hans</creatorcontrib><creatorcontrib>Moritz, Thomas</creatorcontrib><creatorcontrib>La Torre, Daria</creatorcontrib><creatorcontrib>Lernmark, Åke</creatorcontrib><creatorcontrib>Sveriges lantbruksuniversitet</creatorcontrib><title>Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.</description><subject>Analysis</subject><subject>Animals</subject><subject>Annotations</subject><subject>Biology and Life Sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Breeding</subject><subject>Carbohydrates</subject><subject>Care and treatment</subject><subject>Celiac disease</subject><subject>Cell and Molecular Biology</subject><subject>Cell- och molekylärbiologi</subject><subject>Children & youth</subject><subject>Clinical Medicine</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Diabetes Mellitus, Type 1 - blood</subject><subject>Diabetes Mellitus, Type 1 - genetics</subject><subject>Diabetes Mellitus, Type 1 - metabolism</subject><subject>Endocrinology and Diabetes</subject><subject>Endokrinologi och diabetes</subject><subject>Fat metabolism</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Gas Chromatography-Mass Spectrometry</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - 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metabolism</topic><topic>Breeding</topic><topic>Carbohydrates</topic><topic>Care and treatment</topic><topic>Celiac disease</topic><topic>Cell and Molecular Biology</topic><topic>Cell- och molekylärbiologi</topic><topic>Children & youth</topic><topic>Clinical Medicine</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Diabetes Mellitus, Type 1 - blood</topic><topic>Diabetes Mellitus, Type 1 - genetics</topic><topic>Diabetes Mellitus, Type 1 - metabolism</topic><topic>Endocrinology and Diabetes</topic><topic>Endokrinologi och diabetes</topic><topic>Fat metabolism</topic><topic>Fatty acids</topic><topic>Female</topic><topic>Gas Chromatography-Mass Spectrometry</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Hospitals</topic><topic>Hyperglycemia</topic><topic>Hyperglycemia - blood</topic><topic>Hyperglycemia - genetics</topic><topic>Hyperglycemia - metabolism</topic><topic>Hypotheses</topic><topic>Insulin</topic><topic>Insulin - 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It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28192442</pmid><doi>10.1371/journal.pone.0171372</doi><tpages>e0171372</tpages><orcidid>https://orcid.org/0000-0002-6672-8972</orcidid><oa>free_for_read</oa></addata></record> |
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issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1867965922 |
source | MEDLINE; DOAJ Directory of Open Access Journals; SWEPUB Freely available online; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Analysis Animals Annotations Biology and Life Sciences Blood Glucose - metabolism Breeding Carbohydrates Care and treatment Celiac disease Cell and Molecular Biology Cell- och molekylärbiologi Children & youth Clinical Medicine Diabetes Diabetes mellitus Diabetes mellitus (insulin dependent) Diabetes Mellitus, Type 1 - blood Diabetes Mellitus, Type 1 - genetics Diabetes Mellitus, Type 1 - metabolism Endocrinology and Diabetes Endokrinologi och diabetes Fat metabolism Fatty acids Female Gas Chromatography-Mass Spectrometry Gene expression Gene Expression Profiling - methods Hospitals Hyperglycemia Hyperglycemia - blood Hyperglycemia - genetics Hyperglycemia - metabolism Hypotheses Insulin Insulin - metabolism Klinisk medicin Laboratory animals Lipid metabolism Lipid Metabolism - genetics Lipids Liver Liver - metabolism Male Medical and Health Sciences Medicin och hälsovetenskap Medicine and Health Sciences Metabolism Metabolites Metabolome Metabolomics - methods NMR Nuclear magnetic resonance Pancreatic beta cells Physical Sciences Physiological aspects Rats Rats, Inbred BB Rats, Inbred F344 Rodents Signal Transduction - genetics Time Factors Transcriptome - genetics Urine |
title | Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats |
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