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A circadian rhythm-related MTNR1B genetic variant modulates the effect of weight-loss diets on changes in adiposity and body composition: the POUNDS Lost trial

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Abstract

Purpose

A common variant of the melatonin receptor 1B (MTNR1B) gene has been related to increased signaling of melatonin, a hormone previously associated with body fatness mainly through effects on energy metabolism. We examined whether the MTNR1B variant affects changes of body fatness and composition in response to a dietary weight loss intervention.

Methods

The MTNR1B rs10830963 variant was genotyped for 722 overweight and obese individuals, who were randomly assigned to one of four diets varying in macronutrient composition. Anthropometric and body composition measurements (DXA scan) were collected at baseline and at 6 and 24 months of follow-up.

Results

Statistically significant interactions were observed between the MTNR1B genotype and low-/high-fat diet on changes in weight, body mass index (BMI), waist circumference (WC) and total body fat (p interaction = 0.01, 0.02, 0.002 and 0.04, respectively), at 6 months of dietary intervention. In the low-fat diet group, increasing number of the sleep disruption-related G allele was significantly associated with a decrease in weight (p = 0.004), BMI (p = 0.005) and WC (p = 0.001). In the high-fat diet group, carrying the G allele was positively associated with changes in body fat (p = 0.03). At 2 years, the associations remained statistically significant for changes in body weight (p = 0.02), BMI (p = 0.02) and WC (p = 0.048) in the low-fat diet group, although the gene–diet interaction became less significant.

Conclusions

The results suggest that carriers of the G allele of the MTNR1B rs10830963 may have a greater improvement in body adiposity and fat distribution when eating a low-fat diet.

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Acknowledgements

The authors thank all participants of the study for their dedication and contribution to the research. The study is supported by grants from the National Heart, Lung, and Blood Institute (HL-071981, HL-034594, HL-126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK-091718, DK-100383, DK-078616), the Boston Obesity Nutrition Research Center (DK-46200), and United States–Israel Binational Science Foundation Grant 2011036. LG is a recipient of a pre-doctoral and a mobility grant from the Spanish Ministry of Education, Culture and Sport. YH is a recipient of a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science. LQ was a recipient of the American Heart Association Scientist Development Award (0730094N).

Author information

Authors and Affiliations

  1. Department of Nutrition, Food Sciences and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Navarra, Spain

    Leticia Goni & J. Alfredo Martínez

  2. Faculty of Pharmacy and Nutrition, Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain

    Leticia Goni & J. Alfredo Martínez

  3. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA

    Dianjianyi Sun, Yoriko Heianza, Tiange Wang & Lu Qi

  4. Epidemiology Domain, Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Tao Huang

  5. Biomedical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain

    J. Alfredo Martínez

  6. Navarra Institute for Health Research, Pamplona, Navarra, Spain

    J. Alfredo Martínez

  7. Children’s Hospital New Orleans, New Orleans, LA, USA

    Xiaoyun Shang

  8. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA

    George A. Bray & Steven R. Smith

  9. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Frank M. Sacks & Lu Qi

  10. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Lu Qi

  11. Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Lu Qi

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  1. Leticia Goni
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  2. Dianjianyi Sun
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  11. Lu Qi
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Corresponding author

Correspondence to Lu Qi.

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Ethical standards

All procedures of the present study were in accordance with the ethical standards laid down in the 1964 Helsinki declaration and its later amendments. The study was approved by the human subjects committee at each institution and by a data and safety monitoring board appointed by the National Heart, Lung and Blood Institute.

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All participants provided written informed consent.

Conflict of interest

The authors declare that they have no conflict of interest.

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Goni, L., Sun, D., Heianza, Y. et al. A circadian rhythm-related MTNR1B genetic variant modulates the effect of weight-loss diets on changes in adiposity and body composition: the POUNDS Lost trial. Eur J Nutr 58, 1381–1389 (2019). https://doi.org/10.1007/s00394-018-1660-y

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