Ritmos circadianos del tejido adiposo y relación con los hábitos de vida en individuos con obesidad severa

Résumé

Healthy lifestyle habits are crucial for the maintenance of healthy circadian rhythms and for the prevention of alterations in adipose tissue. Studies that address factors that may inhibit or decrease lipolysis directly in human adipose tissue explant cultures are scarce. Therefore, our objectives were: 1) To determine whether circadian rhythms exist in the activity of hormone-sensitive lipase (HSL) and the LIPE gene in human adipose tissue. 1A) To determine whether meal timing and duration of fasting influences LSH activity and LIPE expression. 1B) To determine whether napping is associated with circadian rhythms of LIPE, the gene encoding the LSH enzyme. 2) To determine whether a late dinner affects the insulin sensitivity of human subcutaneous and visceral adipose tissue in the presence of melatonin. 3) To determine whether the effect of time-restricted feeding on human subcutaneous adipose tissue is an effective dietary tool for body weight control. This study was performed in subjects recruited in the region of Murcia, with obesity, who underwent gastric bypass by laparoscopy. Subcutaneous and visceral adipose tissue explants were extracted from these patients for subsequent treatment. Anthropometric measurements were taken, body composition was assessed and the patients' clinical history was collected. As a result of this doctoral thesis we have confirmed the existence of circadian rhythm in human adipose tissue explants in the LIPE gene, and in the activity of LSH, in turn conditioned with the timing of meals and the duration of the overnight fast, which could lead to a greater extent to fat mobilization. This has been achieved by altering the parameters of the rhythms in both the LIPE gene and for the LSH enzyme. In addition, we have shown that napping is a factor altering the rhythmic patterns of the LIPE gene and the LSH protein, demonstrating that those who habitually nap have a flattened rhythm compared to those who do not nap. Likewise, we have shown that naps longer than 30 minutes are associated with a higher waist-hip circumference and metabolic syndrome score, compared to those shorter than 30 minutes. We have also confirmed that insulin sensitivity in human adipose tissue explants is reduced when simultaneously exposed to melatonin and insulin, especially at night. Thus, dinners close to bedtime or the administration of melatonin close to dinner could lead to metabolic problems, such as the development of diabetes and obesity. Finally, we have confirmed that a time-restricted diet is able to mobilize fat to a greater extent than a regular dietary pattern. But we have observed that a greater mobilization of fat occurs when the feeding period is strictly in the morning hours. Therefore, we have concluded that, in order to improve circadian and metabolic health and body weight control in people with obesity, it would be necessary to direct the recommendations towards a meal pattern in accordance with circadian rhythms. Accompanied by advice on the duration of siesta, to reduce alterations in the activity and expression of genes that regulate the mobility of fat, as well as raising awareness of the night schedule or the management of melatonin in relation to dinner time.