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

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.
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.
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.
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.
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.
AuthorsKhadijeh Mirzaei, Min Xu, Qibin Qi, Lilian de Jonge, George A Bray, Frank Sacks, Lu Qi
JournalThe American journal of clinical nutrition (Am J Clin Nutr) Vol. 99 Issue 2 Pg. 392-9 (Feb 2014) ISSN: 1938-3207 [Electronic] United States
PMID24335056 (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
  • 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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: