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

作者:Castellano-Castillo Daniel; Moreno-Indias Isabel; Carlos Fernandez-Garcia Jose; Alcaide-Torres Juan; Moreno-Santos Inmaculada; Ocana Luis; Gluckman Enrique; Tinahones Francisco; Isabel Queipo-Ortuno Maria; Cardona Fernando
来源:Clinical Chemistry, 2018, 64(1): 210-218.
DOI:10.1373/clinchem.2017.277921

摘要

BACKGROUND: 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 di-nucleotides 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

  • 出版日期2018-1