Chronobiology and Obesity: The Orchestra Out of Tune

Marta Garaulet; Purificación Gómez-Abellán; Juan Antonio Madrid


Clin Lipidology. 2010;5(2):181-188. 

In This Article

Nutrigenetics & Chronobiology

Recent research in chronobiology is related to nutrigenetic studies performed in humans. The concept of gene–environment interaction is receiving support from emerging evidence coming primarily from studies involving diet, obesity and its various risk factors. It is generally accepted that common variants in candidate genes for lipid metabolism, inflammation and obesity are associated with altered plasma levels of classic and new biomarkers of the MetS.

With respect to the circadian system, in 2008 Sookoian et al. and Scott et al.[44,45] published for the very first time that different CLOCK gene variants were associated with obesity, particularly with abdominal obesity.[44] In addition, Scott et al. supported the hypothesis that genetic variation in the CLOCK gene may play a role in the development of MetS, Type 2 diabetes and cardiovascular disease.[45]

Later, our own group replicated this data in a North American population Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and in a Mediterranean population derived from southeast Spain. In both populations, four of the five CLOCK single nucleotide polymorphisms (SNPs) studied were related to obesity, to abdominal obesity and to increased energy intake.[46] Moreover, for SNP rs4580704, minor allele carriers demonstrated a 31% less risk of developing diabetes and 46% less risk of suffering from hypertension compared with noncarriers.[47]

In the study performed in the Mediterranean population, the genetic variation in the rs1801260 CLOCK mutations was associated with obesity at baseline and also affected weight loss. Patients with the variant allele (G) demonstrated a higher resistance to weight loss. In this particular polymorphism, the frequency of short-time sleepers (≤6 h per day) was greater in minor allele carriers than in noncarriers (59 vs 41%). Of interest is the interaction observed between CLOCK gene variants and fatty acid composition. We identified significant gene–diet interactions associated to MetS at the CLOCK locus. By dichotomizing monounsaturated fatty acids (MUFAs) intake, we found different effects across rs4580704 genotypes for glucose and insulin resistance. The protective effect of the minor allele on insulin sensitivity was only present when MUFA intake was high. We also found different effects across CLOCK 3111T>C genotypes for saturated fatty acid intake. The deleterious effect of gene variants on waist circumference was only found with high saturated fatty acid intakes.[48] These results suggest that dietary source and membrane content of MUFAs are implicated in the relationship between alterations of circadian system and MetS.


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