New research suggests that variants in two genes involved in regulating circadian rhythms—CRY2 and MTNR1B—also affect changes in energy expenditure during weight loss.

“Our study was motivated by two lines of evidence: first, sleep disorders are related to diabetes mellitus and abnormal glucose metabolism; and second, several genes, such as CRY2 and MTNR1B, are coincidentally related to both sleep (circadian) and glucose metabolism, suggesting potential links exist between them,” explains corresponding author Lu Qi (Harvard School of Public Health, USA). This study was part of the POUNDS LOST trial, a 2-year randomized weight-loss diet intervention trial.

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The researchers genotyped ∼800 patients who were overweight or obese and were randomly assigned to one of four weight-loss diets with different proportions of fats, carbohydrates and protein. Of these patients, 721 were carriers of the CRY2 rs11605924 variant and 722 were carriers of the MTNR1B rs10830963 variant.

Energy expenditure was calculated by measuring respiratory quotient and resting metabolic rate. The A allele of CRY2 rs11605924 was associated with reductions in the respiratory quotient and an increased resting metabolic rate. By contrast, the G allele of MTNR1B rs10830963 was associated with increased respiratory quotient and had no effect on the resting metabolic rate.

Interestingly, it was also found that the genetic effects on energy expenditure were dependent on the level of dietary fat intake. For example, carriers of the A allele of CRY2 rs11605924 on a high-fat diet had a greater reduction in respiratory quotient than did carriers on a low-fat diet.

The researchers acknowledge that their study could be limited by a fairly small sample size, as moderate genetic effects or interactions might not be detected. However, “our data suggest that changes in energy expenditure might link circadian (sleep regulation) and glucose metabolism; and such links might be modulated by dietary fat intake,” says Qi.

The team now aim to validate their findings in other population samples. They are also keen to evaluate the relationship between these circadian-related genes and energy expenditure in animal models.