Periodic Reporting for period 1 - eprObes (Preventing lifetime obesity by early risk-factor identification, prognosis and intervention)
Berichtszeitraum: 2023-05-01 bis 2024-10-31
eprObes is a multidisciplinary, patient-centered project, involving clinical studies targeting different maturational windows, coupled with cognitive, mental health, life-style and behavioral studies, as well as mechanistic analyses in suitable preclinical models, whose major aim is to define effective strategies for active prevention of obesity during the life-course, with particular focus on early developmental events, from prenatal (including peri-conceptional) to pubertal periods, and determinants of feeding behaviors. Multi-omics studies and integral analysis of eprObes data, assisted by bioinformatic technologies and artificial intelligence, will permit definition of tailored preventive measures and life-style interventions, at key maturational periods, to avoid excessive body weight gain and lifetime metabolic complications in both sexes. To achieve these general goals, eprObes is implementing an ambitious research program, organized into 9 interactive work-packages (WP1-9), to be conducted over the 5-year lifespan of the project. As per the first reporting period, the project has been successfully launched and the different WP have been initiated according to the original workplan.
Despite recent progress in the field, treatment options for overweight and obesity in adults remain of limited efficacy. Prevention of obesity in adulthood is also largely unsuccessful, partially due to under-consideration of important determinants of excessive body weight gain at earlier developmental windows. This impedes effective reduction of the prevalence of obesity and its metabolic complications. eprObes departs from the concept that susceptibility to adult obesity is rooted on multiple determinants, either endogenous or environmental, occurring at earlier developmental periods, from periconception to puberty, and is influenced by psycho-social determinants and disorders of feeding behavior occurring mainly at adolescence. While individual contribution of some of these developmental determinants had been fragmentarily defined by different clinical or experimental studies, eprObes will address novel contributing factors, as endometrial signals, changes in blood-brain barrier permeability and epigenetic regulatory mechanisms, and, more importantly, will provide a comprehensive and integral assessment of these determinants, by combining clinical cohort studies, analyzing different windows of development, and preclinical studies in suitable animal models, that will permit a deeper insight into the mechanisms and consequences of these early determinants. Recognition of the full spectrum of such factors will put eprObes in optimal position to define effective preventive strategies, targeting these factors, and tailor early interventions, especially in subsets of subjects with higher risk of developing obesity and its complications.
The main specific objectives of eprObes are as follows:
Objective 1: To set programs of early detection of causal factors related to excessive weight gain during the life-course, with a major focus on early developmental stages and puberty.
Objective 2: To identify the mechanisms underlying causative associations between developmental factors and lifetime obesity, including environmental exposures, epigenetics, and parental and child determinants.
Objective 3: To characterize mental health determinants and feeding behavior alterations, occurring mainly in adolescents and young adults, underlying the propensity to excessive body weight gain.
Objective 4: To identify biomarkers for early detection and prognosis of obesity and associated metabolic complications.
Objective 5: To design and propose tailored preventive strategies and lifestyle interventions for active prevention of excessive weight gain, overweight or obesity, and cardiometabolic complications during the life-course.
Objective 6: To design decision support systems, based on artificial intelligence (AI), to prevent and treat overweight/obesity, under the concept “make it easy to do the right thing.”
Objective 1: To set programs of early detection of causal factors related to excessive weight gain during the life-course, with a major focus on early developmental stages and puberty.
Objective 2: To identify the mechanisms underlying causative associations between developmental factors and lifetime obesity, including environmental exposures, epigenetics, and parental and child determinants.
Objective 3: To characterize mental health determinants and feeding behavior alterations, occurring mainly in adolescents and young adults, underlying the propensity to excessive body weight gain.
Objective 4: To identify biomarkers for early detection and prognosis of obesity and associated metabolic complications.
Objective 5: To design and propose tailored preventive strategies and lifestyle interventions for active prevention of excessive weight gain, overweight or obesity, and cardiometabolic complications during the life-course.
Objective 6: To design decision support systems, based on artificial intelligence (AI), to prevent and treat overweight/obesity, under the concept “make it easy to do the right thing.”