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Altered Adipose Tissue DNA Methylation Status in Metabolic Syndrome: Relationships Between Global DNA Methylation and Specific Methylation at Adipogenic, Lipid Metabolism and Inflammatory Candidate Genes and Metabolic Variables

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Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, 29010 Málaga, Spain
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Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, 28029 Madrid, Spain
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Unidad de Cirugía Metabólica, Hospital Clínico Virgen de la Victoria, 29010 Málaga, Spain
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Unidad de Gestión Clínica de Oncología Médica del Hospital Virgen de la Victoria, 29010 Málaga, Spain
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Authors to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(1), 87; https://doi.org/10.3390/jcm8010087
Received: 4 December 2018 / Revised: 9 January 2019 / Accepted: 10 January 2019 / Published: 13 January 2019
(This article belongs to the Section Endocrinology & Metabolism)
Metabolic syndrome (MetS) has been postulated to increase the risk for type 2 diabetes, cardiovascular disease and cancer. Adipose tissue (AT) plays an important role in metabolic homeostasis, and AT dysfunction has an active role in metabolic diseases. MetS is closely related to lifestyle and environmental factors. Epigenetics has emerged as an interesting landscape to evaluate the possible interconnection between AT and metabolic disease, since it can be modulated by environmental factors and metabolic status. The aim of this study was to determine whether MetS has an impact on the global DNA methylation pattern and the DNA methylation of several genes related to adipogenesis (PPARG, PPARA), lipid metabolism (RXRA, SREBF2, SREBF1, SCD, LPL, LXRb), and inflammation (LRP1 C3, LEP and TNF) in visceral adipose tissue. LPL and TNF DNA methylation values were significantly different in the control-case comparisons, with higher and lower methylation respectively in the MetS group. Negative correlations were found between global DNA methylation (measured by LINE-1 methylation levels) and the metabolic deterioration and glucose levels. There were associations among variables of MetS, BMI, and HOMA-IR with DNA methylation at several CpG positions for the studied genes. In particular, there was a strong positive association between serum triglyceride levels (TG) with PPARA and LPL methylation levels. TNF methylation was negatively associated with the metabolic worsening and could be an important factor in preventing MetS occurrence according to logistic regression analysis. Therefore, global DNA methylation and methylation at specific genes related to adipogenesis, lipid metabolism and inflammation are related to the etiology of MetS and might explain in part some of the features associated to metabolic disorders. View Full-Text
Keywords: epigenetics; DNA methylation; adipose tissue; metabolic syndrome epigenetics; DNA methylation; adipose tissue; metabolic syndrome
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MDPI and ACS Style

Castellano-Castillo, D.; Moreno-Indias, I.; Sanchez-Alcoholado, L.; Ramos-Molina, B.; Alcaide-Torres, J.; Morcillo, S.; Ocaña-Wilhelmi, L.; Tinahones, F.; Queipo-Ortuño, M.I.; Cardona, F. Altered Adipose Tissue DNA Methylation Status in Metabolic Syndrome: Relationships Between Global DNA Methylation and Specific Methylation at Adipogenic, Lipid Metabolism and Inflammatory Candidate Genes and Metabolic Variables. J. Clin. Med. 2019, 8, 87. https://doi.org/10.3390/jcm8010087

AMA Style

Castellano-Castillo D, Moreno-Indias I, Sanchez-Alcoholado L, Ramos-Molina B, Alcaide-Torres J, Morcillo S, Ocaña-Wilhelmi L, Tinahones F, Queipo-Ortuño MI, Cardona F. Altered Adipose Tissue DNA Methylation Status in Metabolic Syndrome: Relationships Between Global DNA Methylation and Specific Methylation at Adipogenic, Lipid Metabolism and Inflammatory Candidate Genes and Metabolic Variables. Journal of Clinical Medicine. 2019; 8(1):87. https://doi.org/10.3390/jcm8010087

Chicago/Turabian Style

Castellano-Castillo, Daniel, Isabel Moreno-Indias, Lidia Sanchez-Alcoholado, Bruno Ramos-Molina, Juan Alcaide-Torres, Sonsoles Morcillo, Luis Ocaña-Wilhelmi, Francisco Tinahones, María I. Queipo-Ortuño, and Fernando Cardona. 2019. "Altered Adipose Tissue DNA Methylation Status in Metabolic Syndrome: Relationships Between Global DNA Methylation and Specific Methylation at Adipogenic, Lipid Metabolism and Inflammatory Candidate Genes and Metabolic Variables" Journal of Clinical Medicine 8, no. 1: 87. https://doi.org/10.3390/jcm8010087

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