TY - JOUR

T1 - Epigenetic and Transcriptomic Characterization of Pure Adipocyte Fractions From Obese Pigs Identifies Candidate Pathways Controlling Metabolism

AU - Jacobsen, Mette Juul

AU - Havgaard, Jakob H.

AU - Anthon, Christian

AU - Mentzel, Caroline M.Junker

AU - Cirera, Susanna

AU - Krogh, Poula Maltha

AU - Pundhir, Sachin

AU - Karlskov-Mortensen, Peter

AU - Bruun, Camilla S.

AU - Lesnik, Philippe

AU - Guerin, Maryse

AU - Gorodkin, Jan

AU - Jørgensen, Claus B.

AU - Fredholm, Merete

AU - Barrès, Romain

PY - 2019

Y1 - 2019

N2 - Reprogramming of adipocyte function in obesity is implicated in metabolic disorders like type 2 diabetes. Here, we used the pig, an animal model sharing many physiological and pathophysiological similarities with humans, to perform in-depth epigenomic and transcriptomic characterization of pure adipocyte fractions. Using a combined DNA methylation capture sequencing and Reduced Representation bisulfite sequencing (RRBS) strategy in 11 lean and 12 obese pigs, we identified in 3529 differentially methylated regions (DMRs) located at close proximity to-, or within genes in the adipocytes. By sequencing of the transcriptome from the same fraction of isolated adipocytes, we identified 276 differentially expressed transcripts with at least one or more DMR. These transcripts were over-represented in gene pathways related to MAPK, metabolic and insulin signaling. Using a candidate gene approach, we further characterized 13 genes potentially regulated by DNA methylation and identified putative transcription factor binding sites that could be affected by the differential methylation in obesity. Our data constitute a valuable resource for further investigations aiming to delineate the epigenetic etiology of metabolic disorders.

AB - Reprogramming of adipocyte function in obesity is implicated in metabolic disorders like type 2 diabetes. Here, we used the pig, an animal model sharing many physiological and pathophysiological similarities with humans, to perform in-depth epigenomic and transcriptomic characterization of pure adipocyte fractions. Using a combined DNA methylation capture sequencing and Reduced Representation bisulfite sequencing (RRBS) strategy in 11 lean and 12 obese pigs, we identified in 3529 differentially methylated regions (DMRs) located at close proximity to-, or within genes in the adipocytes. By sequencing of the transcriptome from the same fraction of isolated adipocytes, we identified 276 differentially expressed transcripts with at least one or more DMR. These transcripts were over-represented in gene pathways related to MAPK, metabolic and insulin signaling. Using a candidate gene approach, we further characterized 13 genes potentially regulated by DNA methylation and identified putative transcription factor binding sites that could be affected by the differential methylation in obesity. Our data constitute a valuable resource for further investigations aiming to delineate the epigenetic etiology of metabolic disorders.

KW - DNA methylation

KW - epigenetics

KW - metabolism

KW - obesity

KW - RNAseq

KW - Sus scrofa

U2 - 10.3389/fgene.2019.01268

DO - 10.3389/fgene.2019.01268

M3 - Journal article

C2 - 31921306

AN - SCOPUS:85077317504

VL - 10

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

M1 - 1268

ER -