Adipose Tissue LPL Methylation is Associated with Triglyceride Concentrations in the Metabolic Syndrome

DNA methylation is one of the epigenetic mechanisms that regulate gene expression. DNA methylation may be modified by environmental and nutritional factors. Thus, epigenetics could potentially provide a mechanism to explain the etiology of metabolic disorders, such as metabolic syndrome (MetS). The...

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Published in:	Clinical chemistry (Baltimore, Md.) Vol. 64; no. 1; pp. 210 - 218
Main Authors:	Castellano-Castillo, Daniel, Moreno-Indias, Isabel, Fernández-García, José Carlos, Alcaide-Torres, Juan, Moreno-Santos, Inmaculada, Ocaña, Luis, Gluckman, Enrique, Tinahones, Francisco, Queipo-Ortuño, María Isabel, Cardona, Fernando
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 01-01-2018
Subjects:	Abnormalities Adipose tissue Adult Anthropometry Blotting, Western Body fat Body Mass Index Case-Control Studies CpG islands Deoxyribonucleic acid Dietary Fats - administration & dosage Disorders DNA DNA Methylation Epigenesis, Genetic Epigenetics Etiology Gene expression Humans Hypertriglyceridemia Insulin resistance Intra-Abdominal Fat - enzymology Laparoscopy Lipase Lipoprotein lipase Lipoprotein Lipase - genetics Lipoprotein Lipase - metabolism Low density lipoprotein Metabolic disorders Metabolic syndrome Metabolic Syndrome - blood Metabolic Syndrome - enzymology Metabolic Syndrome - genetics Metabolism Patients Polymerase Chain Reaction Postprandial Period Promoter Regions, Genetic RNA, Messenger - genetics Triglycerides Triglycerides - blood
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Summary:	DNA methylation is one of the epigenetic mechanisms that regulate gene expression. DNA methylation may be modified by environmental and nutritional factors. Thus, epigenetics could potentially provide a mechanism to explain the etiology of metabolic disorders, such as metabolic syndrome (MetS). The aim of this study was to analyze the level of DNA methylation of several lipoprotein lipase (LPL)-promoter-CpG dinucleotides in a CpG island region and relate this to the gene and protein expression levels in human visceral adipose tissue (VAT) from individuals with and without MetS. VAT samples were collected from laparoscopic surgical patients without and with MetS, and levels of LPL mRNA, LPL protein, and LPL DNA methylation were measured by qPCR, western blot, and pyrosequencing. Biochemical and anthropometric variables were analyzed. Individuals included in a subset underwent a dietary fat challenge test, and levels of postprandial triglycerides were determined. We found higher levels of DNA methylation in MetS patients but lower gene expression and protein levels. There was a negative association between LPL methylation and LPL gene expression. We found a positive association between LPL methylation status and abnormalities of the metabolic profile and basal and postprandial triglycerides, whereas LPL gene expression was negatively associated with these abnormalities. We demonstrate that LPL methylation may be influenced by the degree of metabolic disturbances and could be involved in triglyceride metabolism, promoting hypertriglyceridemia and subsequent associated disorders, such as MetS.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-9147 1530-8561
DOI:	10.1373/clinchem.2017.277921