Changes in DNA Methylation of Clock Genes in Obese Adolescents after a Short-Term Body Weight Reduction Program: A Possible Metabolic and Endocrine Chrono-Resynchronization

• Published in: International journal of environmental research and public health 2022-11, Vol.19 (23), p.15492
• Main Authors: Rigamonti, Antonello E, Bollati, Valentina, Favero, Chiara, Albetti, Benedetta, Caroli, Diana, De Col, Alessandra, Cella, Silvano G, Sartorio, Alessandro
• Format: Article
• Language: English
• Subjects: Adolescent; Adolescents; Adrenocorticotropic hormone; Blood; Blood pressure; Body composition; Body fat; Body mass index; Body weight; C-reactive protein; Cardiovascular system; Child; Cholesterol; Circadian rhythms; Cryptochromes; Deoxyribonucleic acid; DNA; DNA Methylation; Endocrine System; Epigenetics; Exercise; Gene expression; Genes; Heart rate; Homeostasis; Hospitals; Humans; Hypothalamic-pituitary-adrenal axis; Inflammation; Insulin; Lipids; Male; Metabolic disorders; Metabolic syndrome; Obesity; Pediatric Obesity - genetics; Pediatrics; Period 1 protein; Period 2 protein; Period 3 protein; Physical fitness; Pituitary; Proteins; Rehabilitation; Standard scores; Teenagers; Triglycerides; Weight control; Weight Loss; Weight reduction; Weight Reduction Programs
• ISSN: 1660-4601; 1661-7827; 1660-4601
• DOI: 10.3390/ijerph192315492

Circadian rhythms are generated by a series of genes, collectively named genes, which act as a self-sustained internal 24 h timing system in the body. Many physiological processes, including metabolism and the endocrine system, are regulated by genes in coordination with environmental cues. Loss of the circadian rhythms has been reported to contribute to widespread obesity, particularly in the pediatric population, which is increasingly exposed to chronodisruptors in industrialized society. The aim of the present study was to evaluate the DNA methylation status of seven genes, namely , , and , in a cohort of chronobiologically characterized obese adolescents (n: 45: F/M: 28/17; age ± SD: 15.8 ± 1.4 yrs; BMI SDS: 2.94 [2.76; 3.12]) hospitalized for a 3-week multidisciplinary body weight reduction program (BWRP), as well as a series of cardiometabolic outcomes and markers of hypothalamo-pituitary-adrenal (HPA) function. At the end of the intervention, an improvement in body composition was observed (decreases in BMI SDS and fat mass), as well as glucometabolic homeostasis (decreases in glucose, insulin, HOMA-IR and Hb1Ac), lipid profiling (decreases in total cholesterol, LDL-C, triglycerides and NEFA) and cardiovascular function (decreases in systolic and diastolic blood pressures and heart rate). Moreover, the BWRP reduced systemic inflammatory status (i.e., decrease in C-reactive protein) and HPA activity (i.e., decreases in plasma ACTH/cortisol and 24 h urinary-free cortisol excretion). Post-BWRP changes in the methylation levels of , and genes occurred in the entire population, together with hypermethylation of and genes in males and in subjects with metabolic syndrome. In contrast to the pre-BWRP data, at the end of the intervention, cardiometabolic parameters, such as fat mass, systolic and diastolic blood pressures, triglycerides and HDL-C, were associated with the methylation status of some genes. Finally, BWRP induced changes in genes that were associated with markers of HPA function. In conclusion, when administered to a chronodisrupted pediatric obese population, a short-term BWRP is capable of producing beneficial cardiometabolic effects, as well as an epigenetic remodeling of specific genes, suggesting the occurrence of a post-BWRP metabolic and endocrine chronoresynchronization, which might represent a "biomolecular" predictor of successful antiobesity intervention.