Estudio de la relación entre los hábitos de vida, las variaciones del ritmo circadiano y los trastornos metabólicos en la obesidad infantil

Resumen

Numerous studies on nightshift workers evidence a link between circadian rhythms disruption and metabolic disorders. In parallel, other investigations mainly carried out on animal models or in human adults, show a link between the timing of life habits, insufficient duration and poor quality of sleep, and the development of obesity and its comorbidities. Nevertheless, little is known about the role played by these mechanisms in the current epidemic of childhood obesity. Therefore, we developed a study of the relationship between life habits, circadian rhythms of melatonin, and metabolism, in the context of childhood obesity. In complement, we also studied in vitro the impact of melatonin on the circadian rhythm of the genetic expression of adipocytes. M&M: A transversal and analytical study was performed on 203 children between 7 and 16 years old, assigned to the control group or the overweight and obesity group. Anthropometric and clinical characteristics were collected, metabolic and inflammatory markers were measured in the plasma. Melatonin was assessed by immunoassay in saliva that was collected by the participants at home at three time points: 4h before sleep time, 2h before sleep time and after 1h of sleep. Questionnaires were used to collect information about life habits, chronotype, and life environment. The in vitro study was performed on human subcutaneous adipocytes, after 24h in culture with or without melatonin supplementation, RNA was extracted at four time points and quantified by rtqPCR for clock genes and metabolic genes. Results: A lower increase rate of melatonin around sleep time was observed in children with overweight and obesity. In parallel, the in vitro study showed that adipocytes stimulated with melatonin present a greater amplitude in the circadian expression of clock genes and metabolic genes. In children, correlations and multivariate analysis showed interrelationships between variables from all the different categories: anthropometry, clinic, metabolism, inflammation, circadian rhythms, chronotype, life habits, and environment. A subsequent clustering analysis showed that among the individuals from the obesity group, a subgroup of individuals presented a better metabolic health in parallel of earlier life habits and a longer sleep duration. An algorithm showed that, among the parameters studied, poor sleep quality and duration and late meal timing were the strongest predictors of obesity. Another algorithm showed that melatonin nocturnal increase rate was as much a biomarker of obesity as classic markers such as adiponectin, omentin, ghrelin, or glucose. Discussion: The present findings support that there is, in childhood obesity, a relationship between life habits, circadian rhythms of melatonin and metabolism. We observed that late chronotypes and life habits, short sleep duration, poor sleep quality, and eating more in the later part of the day, are associated to poorer metabolic health outcomes, in parallel of an altered nocturnal melatonin rise. Plus, the presence of screen devices in the sleep environment, as well as low education levels of the parents and precarious work situation of the father, appear as risk factors for the children in term of social jetlag, short sleep, late life habit, but also obesity and its metabolic alterations. These new findings emphasize the importance to address sleep, life habits timing, and life environment, in the development of measures of prevention and treatment of obesity.