Ghrelin, Sleep Reduction and Evening Preference: Relationships to CLOCK 3111 T/C SNP and Weight Loss

Abstract

Background Circadian Locomotor Output Cycles Kaput (CLOCK), an essential element of the positive regulatory arm in the human biological clock, is involved in metabolic regulation. The aim was to investigate the behavioral (sleep duration, eating patterns and chronobiological characteristics) and hormonal (plasma ghrelin and leptin concentrations) factors which could explain the previously reported association between the CLOCK 3111T/C SNP and weight loss.Methodology/Principal FindingsWe recruited 1495 overweight/obese subjects (BMI: 25–40 kg/m2) of 20–65 y. who attended outpatient obesity clinics in Murcia, in southeastern Spain. We detected an association between the CLOCK 3111T/C SNP and weight loss, which was particularly evident after 12–14 weeks of treatment (P = 0.038). Specifically, carriers of the minor C allele were more resistant to weight loss than TT individuals (Mean±SEM) (8.71±0.59 kg vs 10.4±0.57 kg) C and TT respectively. In addition, our data show that minor C allele carriers had: 1. shorter sleep duration Mean ± SEM (7.0±0.05 vs 7.3±0.05) C and TT respectively (P = 0.039), 2. higher plasma ghrelin concentrations Mean ± SEM (pg/ml) (1108±49 vs 976±47)(P = 0.034); 3. delayed breakfast time; 4. evening preference and 5. less compliance with a Mediterranean Diet pattern, as compared with TT homozygotes.Conclusions/SignificanceSleep reduction, changes in ghrelin values, alterations of eating behaviors and evening preference that characterized CLOCK 3111C carriers could be affecting weight loss. Our results support the hypothesis that the influence of the CLOCK gene may extend to a broad range of variables linked with human behaviors.

Chronobiology and Obesity

“…Of note, these new data related to DNA methylation are consistent with previous results related to CLOCK genetic variants, which demonstrated that sleep reduction, changes in ghrelin values, alterations of eating behaviors and evening preference are all connecting genetics, chronodisruption and obesity. 34 These results support the hypothesis that the influence of the clock genes may be extended to a broad range of variables linked with human behavior and metabolism. Moreover, our data pave the way to the study of epigenetic mechanisms in the regulation of circadian rhythms in relation to obesity and weight loss.…”

“…[32][33][34][35][36][37][38][39][40][41] Indeed, obesity is a heterogeneous condition and individual responses to standardized protocols targeting weight loss are highly variable. 2 In real life settings such as obesity treatment programs, physiological and psychological factors, some of which may carry a strong ge netic influence, interact with environmental factors in a complex manner.…”

“…46,47 Moreover, different psychological traits have been related to CLOCK 3111T > C SNP. 48,49 The association with psychological illnesses is related to the fact that minor allele carriers of CLOCK 3111TC display sleep disorders and eveningness, 34 characteristics that, in addition, make these subjects susceptible to obesity.…”

Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals

“…Clock and Bmal1 gene polymorphisms in humans suggest that genetic variation in these genes may play a role in the development of obesity and type 2 diabetes (Scott et al, 2008;Sookoian et al, 2008;Woon et al, 2007). Single-nucleotide polymorphisms (SNPs) in CLOCK are correlated with elevated plasma ghrelin levels, reduced sleep duration and increased energy intake (Garaulet et al, 2010(Garaulet et al, , 2011. Furthermore, carriers of CLOCK SNPs display lower plasma glucose concentrations and improved insulin sensitivity when they eat a diet rich in mono-unsaturated fatty acids Garcia-Rios et al, 2014).…”

The Role of Sleep Duration in the Regulation of Energy Balance: Effects on Energy Intakes and Expenditure

“…Garaulet et al 40 reported associations between CLOCK3111T/C allele genotype and ghrelin but not leptin levels. Individuals who were carriers of the C allele had higher ghrelin levels than those with TT genotype.…”