Epigenetic Regulation of PLIN 1 in Obese Women and its Relation to Lipolysis

• Published in: Scientific reports Vol. 7; no. 1; p. 10152
• Main Authors: Bialesova, Lucia, Kulyté, Agné, Petrus, Paul, Sinha, Indranil, Laurencikiene, Jurga, Zhao, Chunyan, Wright, Karin Dahlman, Arner, Peter, Dahlman, Ingrid
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 31.08.2017
• Subjects: Adipocytes; Adipocytes, White - cytology; Adipocytes, White - metabolism; Adipose tissue; Adult; CpG Islands; DNA Methylation; DNA methyltransferase; Epigenesis, Genetic; Epigenetics; Explants; Female; Gene expression; Glycerol; Glycerol - metabolism; Humans; Insulin; Insulin resistance; Lipolysis; Medicin och hälsovetenskap; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Middle Aged; Obesity; Obesity - genetics; Obesity - metabolism; Perilipin-1 - genetics; Perilipin-1 - metabolism; Reporter gene; Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-09232-y

Increased adipocyte lipolysis links obesity to insulin resistance. The lipid droplet coating-protein Perilipin participates in regulation of lipolysis and is implicated in obesity. In the present study we investigate epigenetic regulation of the PLIN1 gene by correlating PLIN1 CpG methylation to gene expression and lipolysis, and functionally evaluating PLIN1 promoter methylation. PLIN1 CpG methylation in adipocytes and gene expression in white adipose tissue (WAT) was quantified in two cohorts by array. Basal lipolysis in WAT explants and adipocytes was quantified by measuring glycerol release. CpG-methylation of the PLIN1 promoter in adipocytes from obese women was higher as compared to never-obese women. PLIN1 promoter methylation was inversely correlated with PLIN1 mRNA expression and the lipolytic activity. Human mesenchymal stem cells (hMSCs) differentiated in vitro into adipocytes and harboring methylated PLIN1 promoter displayed decreased reporter gene activity as compared to hMSCs harboring unmethylated promoter. Treatment of hMSCs differentiated in vitro into adipocytes with a DNA methyltransferase inhibitor increased levels of PLIN1 mRNA and protein. In conclusion, the PLIN1 gene is epigenetically regulated and promoter methylation is inversely correlated with basal lipolysis in women suggesting that epigenetic regulation of PLIN1 is important for increased adipocyte lipolysis in insulin resistance states.