Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial.

Abstract

BACKGROUND:

Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes, probably through effects on energy balance. Recent genome-wide association studies identified variants in circadian rhythm-related genes (CRY2 and MTNR1B) associated with glucose homeostasis.

OBJECTIVE:

We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST Trial.

DESIGN:

The variants CRY2 rs11605924 (n = 721) and MTNR1B rs10830963 (n = 722) were genotyped in overweight or obese adults who were randomly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients. Respiratory quotient (RQ) and resting metabolic rate (RMR) were measured.

RESULTS:

By 2 y of diet intervention, the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ (P = 0.03) and a greater increase in RMR and RMR/kg (both P = 0.04). The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ (P = 0.01) but was not related to changes in RMR and RMR/kg. In addition, we found significant gene-diet fat interactions for both CRY2 (P-interaction = 0.02) and MTNR1B (P-interaction < 0.001) in relation to 2-y changes in RQ.

CONCLUSIONS:

Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure, and dietary fat intake may modify the genetic effects. This trial was registered at www.clinicaltrials.gov as NCT00072995.

• Authors: Khadijeh Mirzaei, Min Xu, Qibin Qi, Lilian de Jonge, George A Bray, Frank Sacks, Lu Qi
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 99 Issue 2 Pg. 392-9 (Feb 2014) ISSN: 1938-3207 [Electronic] United States
• PMID: 24335056 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Blood Glucose
• CRY2 protein, human
• Cryptochromes
• MTNR1B protein, human
• Receptor, Melatonin, MT1
• Receptor, Melatonin, MT2

Topics

• Adult
• Aged
• Alleles
• Basal Metabolism
• Blood Glucose (genetics, metabolism)
• Circadian Rhythm (genetics)
• Cryptochromes (genetics, metabolism)
• Diet, Reducing
• Energy Metabolism
• Female
• Genetic Loci
• Genome-Wide Association Study
• Genotype
• Homeostasis (genetics)
• Humans
• Linear Models
• Male
• Middle Aged
• Obesity (diet therapy, genetics)
• Overweight (diet therapy, genetics)
• Polymorphism, Single Nucleotide
• Prospective Studies
• Receptor, Melatonin, MT1 (genetics, metabolism)
• Receptor, Melatonin, MT2