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Complement Factor C3 Methylation and mRNA Expression Is Associated to BMI and Insulin Resistance in Obesity

Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Malaga, 29010 Malaga, Spain
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBERobn), 28029 Madrid, Spain
Department of Internal Medicine Center for Endocrinology, Diabetes and Vascular Medicine St. Franciscus Gasthuis Hospital, 3045 PM Rotterdam, The Netherlands
Author to whom correspondence should be addressed.
These authors have contributed in the same way to this work.
Genes 2018, 9(8), 410;
Received: 21 June 2018 / Revised: 20 July 2018 / Accepted: 8 August 2018 / Published: 13 August 2018
(This article belongs to the Special Issue Advances in Genetics of Regeneration in Metabesity)
PDF [358 KB, uploaded 14 August 2018]


Epigenetic marks, and especially DNA methylation, are becoming an important factor in obesity, which could help to explain its etiology and associated comorbidities. Adipose tissue, now considered as an important endocrine organ, produces complement system factors. Complement component 3 (C3) turns out to be an important protein in metabolic disorders, via either inflammation or the C3 subproduct acylation stimulating protein (ASP) which directly stimulates lipid storage. In this study, we analyze C3 DNA methylation in adipose tissue from subjects with a different grade of obesity. Adipose tissue samples were collected from subjects with a different degree of obesity determined by their body mass index (BMI) as: Overweight subjects (BMI ≥ 25 and <30), obese class 1/2 subjects (BMI ≥ 30 and <40) and obese class 3 subjects (BMI ≥ 40). C3 DNA methylation was measured for 7 CpGs by pyrosequencition using the Pyromark technology (Qiagen, Madrid Spain). C3 messenger RNA (mRNA) levels were analyzed by pre-designed Taqman assays (Applied biosystems, Foster City, CA, USA) and ASP/C3a was measured using a ELISA kit. The data were analyzed using the statistic package SPSS. C3 DNA methylation levels were lower in the morbid obese group. Accordingly, C3 methylation correlated negatively with BMI and leptin. However, C3 mRNA levels were more associated with insulin resistance, and positive correlations with insulin, glucose and homeostasis model assessment-estimated insulin resistance (HOMA-IR) existed. ASP correlated negatively with high density lipoprotein (HDL) cholesterol. C3 methylation levels were associated to adiposity variables, such as BMI and leptin, while the C3 mRNA levels were associated to glucose metabolism. View Full-Text
Keywords: DNA methylation; C3; ASP; complement factor; obesity; insulin resistance DNA methylation; C3; ASP; complement factor; obesity; insulin resistance

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Castellano-Castillo, D.; Moreno-Indias, I.; Fernandez-Garcia, J.C.; Clemente-Postigo, M.; Castro-Cabezas, M.; Tinahones, F.J.; Queipo-Ortuño, M.I.; Cardona, F. Complement Factor C3 Methylation and mRNA Expression Is Associated to BMI and Insulin Resistance in Obesity. Genes 2018, 9, 410.

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