{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/99124"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/99124","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"High fat diet causes hepatic lipid accumulation by programming lipid synthesizing genes via gene body methylation","abstract":"A high-fat diet (HFD) has been shown to cause more hepatic lipid accumulation as compared to a low-fat control (C) diet. However, it is still unclear what role epigenetic mechanisms play in hepatic lipid accumulation. We hypothesize that a HFD will cause greater hepatic lipid accumulation through increased lipid synthesizing gene expression via decreased gene methylation. The objective of this study is to determine the role of methylation in hepatic lipid synthesizing genes as an outcome of hepatic lipid accumulation due to a HFD. Two models were used to address the following: the direct effects of a post-weaning HFD on hepatic lipid synthesizing genes as well as the indirect effects of a maternal HFD. Timed-pregnant Sprague-Dawley rats were given either a C (16% fat) or HFD (45% fat) during gestation and lactation. Pups from both C mothers were weaned onto either a C or HFD and the pups from the maternal HFD were weaned onto a HFD, creating three offspring groups: C/C, C/HF, and HF/HF. Model 1 compared the C/C group to the C/HF group, while model 2 focused on the comparison of the C/HF group to the HF/HF group. Rats were sacrificed at 12 weeks of age, and the left lobe of the liver was used for further analysis. In model 1, liver histology showed greater hepatic fat accumulation in the C/HF group. Gene expression data was measured for multiple genes in the following pathways: glycolysis, gluconeogenesis, fatty acid synthesis, and triacylglycerol synthesis. Glycerol-3-phosphate acyltransferase (GPAM), fatty acid synthase (FASN), acetyl CoA carboxylase 1 (ACC1), and glucose-6-phosphotase (G6Pase) showed lower levels of mRNA in the C/HF group as compared to the C/C group. DNA methylation of those genes was analyzed based on data obtained from methyl-DNA immunoprecipitation with high-throughput sequencing (MEDIP-SEQ). Differential methylation was observed for G6Pase, GPAM, and ACC1. GPAM and ACC1 showed decreased average methylation read peaks for C/HF in comparison to the C/C group. The data in model 1 suggest that decreased gene body methylation leads to decreased lipid synthesizing genes. In model 2, liver histology showed greater hepatic fat accumulation in the HF/HF group. Gene expression data were measured in the same pathways as previously stated. GPAM and FASN showed higher levels of mRNA in the HF/HF group. MEDIP-SEQ data showed greater average methylations read peaks for HF/HF along the gene body for GPAM. Methylation specific polymerase chain reaction (MSP) validated these results by showing greater methylation on intron 1, on the 7.2 kilobases (kB) pair region, as well as exon 21, at 59.5 kB pair region on GPAM. The data in model 2 suggest that increased gene body methylation leads to increased lipid synthesizing genes. These studies suggest that there is a positive relationship between gene body methylation and mRNA expression in hepatic lipid synthesizing genes.","abstract_html":"A high-fat diet (HFD) has been shown to cause more hepatic lipid accumulation as compared to a low-fat control (C) diet. However, it is still unclear what role epigenetic mechanisms play in hepatic lipid accumulation. We hypothesize that a HFD will cause greater hepatic lipid accumulation through increased lipid synthesizing gene expression via decreased gene methylation. The objective of this study is to determine the role of methylation in hepatic lipid synthesizing genes as an outcome of hepatic lipid accumulation due to a HFD. Two models were used to address the following: the direct effects of a post-weaning HFD on hepatic lipid synthesizing genes as well as the indirect effects of a maternal HFD. Timed-pregnant Sprague-Dawley rats were given either a C (16% fat) or HFD (45% fat) during gestation and lactation. Pups from both C mothers were weaned onto either a C or HFD and the pups from the maternal HFD were weaned onto a HFD, creating three offspring groups: C/C, C/HF, and HF/HF. Model 1 compared the C/C group to the C/HF group, while model 2 focused on the comparison of the C/HF group to the HF/HF group. Rats were sacrificed at 12 weeks of age, and the left lobe of the liver was used for further analysis. In model 1, liver histology showed greater hepatic fat accumulation in the C/HF group. Gene expression data was measured for multiple genes in the following pathways: glycolysis, gluconeogenesis, fatty acid synthesis, and triacylglycerol synthesis. Glycerol-3-phosphate acyltransferase (GPAM), fatty acid synthase (FASN), acetyl CoA carboxylase 1 (ACC1), and glucose-6-phosphotase (G6Pase) showed lower levels of mRNA in the C/HF group as compared to the C/C group. DNA methylation of those genes was analyzed based on data obtained from methyl-DNA immunoprecipitation with high-throughput sequencing (MEDIP-SEQ). Differential methylation was observed for G6Pase, GPAM, and ACC1. GPAM and ACC1 showed decreased average methylation read peaks for C/HF in comparison to the C/C group. The data in model 1 suggest that decreased gene body methylation leads to decreased lipid synthesizing genes. In model 2, liver histology showed greater hepatic fat accumulation in the HF/HF group. Gene expression data were measured in the same pathways as previously stated. GPAM and FASN showed higher levels of mRNA in the HF/HF group. MEDIP-SEQ data showed greater average methylations read peaks for HF/HF along the gene body for GPAM. Methylation specific polymerase chain reaction (MSP) validated these results by showing greater methylation on intron 1, on the 7.2 kilobases (kB) pair region, as well as exon 21, at 59.5 kB pair region on GPAM. The data in model 2 suggest that increased gene body methylation leads to increased lipid synthesizing genes. These studies suggest that there is a positive relationship between gene body methylation and mRNA expression in hepatic lipid synthesizing genes.","abstract_has_math":false,"creators":["Jung, Paul M"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Food Science & Human Nutrition","degree_department":null,"school":null,"contributors":["Pan, Yuan-Xiang","Chen, Hong","Miller, Michael J."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-03-02T19:59:46Z","date_published":"2018-03-02T19:59:46Z","updated_at":"2026-07-22T22:24:37Z","subjects":["Epigenetics","Nutrient-gene interaction","Nonalcoholic fatty liver disease","Obesity"],"languages":["en"],"rights":["Copyright 2017 Paul Jung"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/99124","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Pan, Yuan-Xiang","Chen, Hong","Miller, Michael J."]},{"key":"dc:creator","label":"Author","values":["Jung, Paul M"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-03-02T19:59:46Z","2020-03-03T10:15:32Z","2017-07-20","2017-08"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Food Science & Human Nutrition"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Epigenetics","Nutrient-gene interaction","Nonalcoholic fatty liver disease","Obesity"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2017 Paul Jung"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/99124"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["A high-fat diet (HFD) has been shown to cause more hepatic lipid accumulation as compared to a low-fat control (C) diet. However, it is still unclear what role epigenetic mechanisms play in hepatic lipid accumulation. We hypothesize that a HFD will cause greater hepatic lipid accumulation through increased lipid synthesizing gene expression via decreased gene methylation. The objective of this study is to determine the role of methylation in hepatic lipid synthesizing genes as an outcome of hepatic lipid accumulation due to a HFD. Two models were used to address the following: the direct effects of a post-weaning HFD on hepatic lipid synthesizing genes as well as the indirect effects of a maternal HFD. Timed-pregnant Sprague-Dawley rats were given either a C (16% fat) or HFD (45% fat) during gestation and lactation. Pups from both C mothers were weaned onto either a C or HFD and the pups from the maternal HFD were weaned onto a HFD, creating three offspring groups: C/C, C/HF, and HF/HF. Model 1 compared the C/C group to the C/HF group, while model 2 focused on the comparison of the C/HF group to the HF/HF group. Rats were sacrificed at 12 weeks of age, and the left lobe of the liver was used for further analysis. In model 1, liver histology showed greater hepatic fat accumulation in the C/HF group. Gene expression data was measured for multiple genes in the following pathways: glycolysis, gluconeogenesis, fatty acid synthesis, and triacylglycerol synthesis. Glycerol-3-phosphate acyltransferase (GPAM), fatty acid synthase (FASN), acetyl CoA carboxylase 1 (ACC1), and glucose-6-phosphotase (G6Pase) showed lower levels of mRNA in the C/HF group as compared to the C/C group. DNA methylation of those genes was analyzed based on data obtained from methyl-DNA immunoprecipitation with high-throughput sequencing (MEDIP-SEQ). Differential methylation was observed for G6Pase, GPAM, and ACC1. GPAM and ACC1 showed decreased average methylation read peaks for C/HF in comparison to the C/C group. The data in model 1 suggest that decreased gene body methylation leads to decreased lipid synthesizing genes. In model 2, liver histology showed greater hepatic fat accumulation in the HF/HF group. Gene expression data were measured in the same pathways as previously stated. GPAM and FASN showed higher levels of mRNA in the HF/HF group. MEDIP-SEQ data showed greater average methylations read peaks for HF/HF along the gene body for GPAM. Methylation specific polymerase chain reaction (MSP) validated these results by showing greater methylation on intron 1, on the 7.2 kilobases (kB) pair region, as well as exon 21, at 59.5 kB pair region on GPAM. The data in model 2 suggest that increased gene body methylation leads to increased lipid synthesizing genes. These studies suggest that there is a positive relationship between gene body methylation and mRNA expression in hepatic lipid synthesizing genes.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2019-08-01","The student, Paul Jung, accepted the attached license on 2017-07-19 at 10:44.","The student, Paul Jung, submitted this Thesis for approval on 2017-07-19 at 10:59.","This Thesis was approved for publication on 2017-07-20 at 10:24.","DSpace SAF Submission Ingestion Package generated from Vireo submission #11525 on 2018-03-02 at 13:02:39","Made available in DSpace on 2018-03-02T19:59:46Z (GMT). No. of bitstreams: 3 JUNG-THESIS-2017.pdf: 2162430 bytes, checksum: 37cc8af9f11e18a73531513e2785e462 (MD5) 20170719 Thesis Writing PMJ.docx: 3270975 bytes, checksum: 1d791d0e2e0479a855d43987c797d9a7 (MD5) LICENSE.txt: 4206 bytes, checksum: 1e2517a7b12f8eee7483848fe2180b44 (MD5) Previous issue date: 2017-07-20","Embargo set by: Seth Robbins for item 105078 Lift date: 2020-03-02T19:59:52Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 105078 Lift date: 2020-03-02T20:02:46Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only Restriction Lifted for Item 105078 on 2020-03-03T10:15:32Z."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["High fat diet causes hepatic lipid accumulation by programming lipid synthesizing genes via gene body methylation"]}]}],"canonical_facts":{"dc:contributor":["Pan, Yuan-Xiang","Chen, Hong","Miller, Michael J."],"dc:creator":["Jung, Paul M"],"dc:date":["2018-03-02T19:59:46Z","2020-03-03T10:15:32Z","2017-07-20","2017-08"],"dc:description":["A high-fat diet (HFD) has been shown to cause more hepatic lipid accumulation as compared to a low-fat control (C) diet. However, it is still unclear what role epigenetic mechanisms play in hepatic lipid accumulation. We hypothesize that a HFD will cause greater hepatic lipid accumulation through increased lipid synthesizing gene expression via decreased gene methylation. The objective of this study is to determine the role of methylation in hepatic lipid synthesizing genes as an outcome of hepatic lipid accumulation due to a HFD. Two models were used to address the following: the direct effects of a post-weaning HFD on hepatic lipid synthesizing genes as well as the indirect effects of a maternal HFD. Timed-pregnant Sprague-Dawley rats were given either a C (16% fat) or HFD (45% fat) during gestation and lactation. Pups from both C mothers were weaned onto either a C or HFD and the pups from the maternal HFD were weaned onto a HFD, creating three offspring groups: C/C, C/HF, and HF/HF. Model 1 compared the C/C group to the C/HF group, while model 2 focused on the comparison of the C/HF group to the HF/HF group. Rats were sacrificed at 12 weeks of age, and the left lobe of the liver was used for further analysis. In model 1, liver histology showed greater hepatic fat accumulation in the C/HF group. Gene expression data was measured for multiple genes in the following pathways: glycolysis, gluconeogenesis, fatty acid synthesis, and triacylglycerol synthesis. Glycerol-3-phosphate acyltransferase (GPAM), fatty acid synthase (FASN), acetyl CoA carboxylase 1 (ACC1), and glucose-6-phosphotase (G6Pase) showed lower levels of mRNA in the C/HF group as compared to the C/C group. DNA methylation of those genes was analyzed based on data obtained from methyl-DNA immunoprecipitation with high-throughput sequencing (MEDIP-SEQ). Differential methylation was observed for G6Pase, GPAM, and ACC1. GPAM and ACC1 showed decreased average methylation read peaks for C/HF in comparison to the C/C group. The data in model 1 suggest that decreased gene body methylation leads to decreased lipid synthesizing genes. In model 2, liver histology showed greater hepatic fat accumulation in the HF/HF group. Gene expression data were measured in the same pathways as previously stated. GPAM and FASN showed higher levels of mRNA in the HF/HF group. MEDIP-SEQ data showed greater average methylations read peaks for HF/HF along the gene body for GPAM. Methylation specific polymerase chain reaction (MSP) validated these results by showing greater methylation on intron 1, on the 7.2 kilobases (kB) pair region, as well as exon 21, at 59.5 kB pair region on GPAM. The data in model 2 suggest that increased gene body methylation leads to increased lipid synthesizing genes. These studies suggest that there is a positive relationship between gene body methylation and mRNA expression in hepatic lipid synthesizing genes.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2019-08-01","The student, Paul Jung, accepted the attached license on 2017-07-19 at 10:44.","The student, Paul Jung, submitted this Thesis for approval on 2017-07-19 at 10:59.","This Thesis was approved for publication on 2017-07-20 at 10:24.","DSpace SAF Submission Ingestion Package generated from Vireo submission #11525 on 2018-03-02 at 13:02:39","Made available in DSpace on 2018-03-02T19:59:46Z (GMT). No. of bitstreams: 3 JUNG-THESIS-2017.pdf: 2162430 bytes, checksum: 37cc8af9f11e18a73531513e2785e462 (MD5) 20170719 Thesis Writing PMJ.docx: 3270975 bytes, checksum: 1d791d0e2e0479a855d43987c797d9a7 (MD5) LICENSE.txt: 4206 bytes, checksum: 1e2517a7b12f8eee7483848fe2180b44 (MD5) Previous issue date: 2017-07-20","Embargo set by: Seth Robbins for item 105078 Lift date: 2020-03-02T19:59:52Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 105078 Lift date: 2020-03-02T20:02:46Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only Restriction Lifted for Item 105078 on 2020-03-03T10:15:32Z."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/99124"],"dc:language":["en"],"dc:rights":["Copyright 2017 Paul Jung"],"dc:subject":["Epigenetics","Nutrient-gene interaction","Nonalcoholic fatty liver disease","Obesity"],"dc:title":["High fat diet causes hepatic lipid accumulation by programming lipid synthesizing genes via gene body methylation"],"dc:type":["text"],"thesis:degree_discipline":["Food Science & Human Nutrition"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["M.S."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:37Z"}