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1 From the Nutraceuticals and Functional Foods Institute (LB, LP, and M-CV), the Department of Preventive Medicine (LP), and the Department of Food Science and Nutrition (M-CV), Université Laval, Laval, Canada; the Department of Medicine, Université de Montréal, Chicoutimi Hospital, Saguenay, Canada (LB); the Department of Nutrition (RR-L, MF, and M-EL), the Montreal Diabetes Research Centre (RR-L and MF), Université de Montréal, Montreal, Canada; and the Institute of Psychiatry, SGDP Research Centre, King’s College London, London, United Kingdom (JM).
2 Supported by the Canadian Institute of Health Research through the MONET project (Montreal-Ottawa New Emerging Team; OHN-63279 and MOP62976) and the Quebec New Emerging Team (OHN 63276). LB was funded by the Laval University Merck Frosst/Canadian Institute of Health Research Chair in Obesity and the Heart and Stroke Foundation of Canada/Sanofi-Aventis research fellowship awards. RRL was supported by the Fonds de la Recherche en Santé du Québec and held the chair for clinical research J-A de Sève at IRCM (Montreal Institute for Clinical Research). MF was the recipient of the Canadian Institute of Health Research New Investigator Award. M-EL was supported by a scholarship from the Fonds de la Recherche en Santé du Québec. 3 Address correspondence to M-C Vohl, Lipid Research Center, 2705 Laurier Boulevard, (TR93), Québec City, PQ, Canada G1V 4G2. E-mail: marie-claude.vohl{at}crchul.ulaval.ca.
ABSTRACT
Background: Caloric restriction is recommended for the treatment of obesity, but it is generally characterized by large interindividual variability in responses. The factors affecting the magnitude of weight loss remain poorly understood. Epigenetic factors (ie, heritable but reversible changes to genomic function that regulate gene expression independently of DNA sequence) may explain some of the interindividual variability seen in weight-loss responses.
Objective: The objective was to determine whether epigenetics and gene expression changes may play a role in weight-loss responsiveness.
Design: Overweight/obese postmenopausal women were recruited for a standard 6-mo caloric restriction intervention. Abdominal subcutaneous adipose tissue biopsy samples were collected before (n = 14) and after (n = 14) intervention, and the epigenomic and transcriptomic profiles of the high and low responders to dieting, on the basis of changes in percentage body fat, were compared by using microarray analysis.
Results: Significant DNA methylation differences at 35 loci were found between the high and low responders before dieting, with 3 regions showing differential methylation after intervention. Some of these regions contained genes known to be involved in weight control and insulin secretion, whereas others were localized in known imprinted genomic regions. Differences in gene expression profiles were observed only after dieting, with 644 genes being differentially expressed between the 2 groups. These included genes likely to be involved in metabolic pathways related to angiogenesis and cerebellar long-term depression.
Conclusions: These data show that both DNA methylation and gene expression are responsive to caloric restriction and provide new insights about the molecular pathways involved in body weight loss as well as methylation regulation during adulthood.
Received for publication May 18, 2009. Accepted for publication November 2, 2009.
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