title: Methylation on the Circadian Gene BMAL1 Is Associated with the Effects of a Weight Loss Intervention on Serum Lipid Levels.
abstract: The circadian clock system has been linked to the onset and development of obesity and some accompanying comorbidities. Epigenetic mechanisms, such as DNA methylation, are putatively involved in the regulation of the circadian clock system. The aim of this study was to investigate the influence of a weight loss intervention based on an energy-controlled Mediterranean dietary pattern in the methylation levels of 3 clock genes, BMAL1, CLOCK, and NR1D1, and the association between the methylation levels and changes induced in the serum lipid profile with the weight loss treatment. The study sample enrolled 61 women (body mass index = 28.6 ± 3.4 kg/m(2); age: 42.2 ± 11.4 years), who followed a nutritional program based on a Mediterranean dietary pattern. DNA was isolated from whole blood obtained at the beginning and end point. Methylation levels at different CpG sites of BMAL1, CLOCK, and NR1D1 were analyzed by Sequenom's MassArray. The energy-restricted intervention modified the methylation levels of different CpG sites in BMAL1 (CpGs 5, 6, 7, 9, 11, and 18) and NR1D1 (CpGs 1, 10, 17, 18, 19, and 22). Changes in cytosine methylation in the CpG 5 to 9 region of BMAL1 with the intervention positively correlated with the eveningness profile (p = 0.019). The baseline methylation of the CpG 5 to 9 region in BMAL1 positively correlated with energy (p = 0.047) and carbohydrate (p = 0.017) intake and negatively correlated with the effect of the weight loss intervention on total cholesterol (p = 0.032) and low-density lipoprotein cholesterol (p = 0.005). Similar significant and positive correlations were found between changes in methylation levels in the CpG 5 to 9 region of BMAL1 due to the intervention and changes in serum lipids (p < 0.05). This research describes apparently for the first time an association between changes in the methylation of the BMAL1 gene with the intervention and the effects of a weight loss intervention on blood lipids levels.
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain.
authors.forename: Mirian
authors.initials: M
authors.lastname: Samblas
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain Centre for Nutrition Research, University of Navarra, Pamplona, Spain CIBERobn, Physiopathology of Obesity, Carlos III Institute, Madrid, Spain.
authors.forename: Fermin I
authors.initials: FI
authors.lastname: Milagro
authors.affiliation: Department of Physiology, Faculty of Biology, University of Murcia, IMIB, Murcia, Spain.
authors.forename: Purificación
authors.initials: P
authors.lastname: Gómez-Abellán
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain Centre for Nutrition Research, University of Navarra, Pamplona, Spain CIBERobn, Physiopathology of Obesity, Carlos III Institute, Madrid, Spain IdiSNA, Navarra's Health Research Institute, Pamplona, Spain jalfmtz@unav.es.
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Department of Physiology, Faculty of Biology, University of Murcia, IMIB, Murcia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Garaulet
mesh_terms: D056930:ARNTL Transcription Factors / Q000737:chemistry* / Q000235:genetics*; D000328:Adult; D056926:CLOCK Proteins / Q000737:chemistry / Q000235:genetics; D002784:Cholesterol / Q000097:blood*; D002940:Circadian Rhythm / Q000235:genetics*; D038441:Diet, Mediterranean; D057890:Epigenomics; D005260:Female; D006801:Humans; D008745:Methylation; D008875:Middle Aged; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000737:chemistry / Q000235:genetics; D009765:Obesity; D009838:Oligodeoxyribonucleotides; D014280:Triglycerides / Q000097:blood*; D015431:Weight Loss / Q000235:genetics*
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; C064353:NR1D1 protein, human; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D009838:Oligodeoxyribonucleotides; D014280:Triglycerides; D002784:Cholesterol; D056926:CLOCK Proteins; C538943:CLOCK protein, human
keywords: NR1D1; cholesterol; clock; epigenetics; obesity; triglycerides