Coppola, Serena (2026) ULTRA-PROCESSED FOODS: CLINICAL AND MECHANISTIC INSIGHTS INTO PEDIATRIC OBESITY AND IMMUNOMETABOLIC DYSFUNCTION. [Tesi di dottorato]

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Abstract

Prevalence of pediatric obesity increased dramatically in the last decades at global level. This condition is the main driver of a cluster of metabolic alterations, defined as Metabolic Syndrome (MetS), that increase the risk of cardiovascular diseases and diabetes mellitus, reduce life expectancy and impact significantly healthcare costs. Altough obesity does not necessarily led to MetS, which subjects are most prone to develop MetS remains to be fully elucidated. The worldwide increase in pediatric obesity and MetS has coincided with a shift in dietary patterns from traditional staple foods to ultra-processed foods (UPFs), prompting growing scientific interest in UPFs as potential contributors to the obesity epidemic and associated metabolic disorders. As defined by the NOVA food classification system, UPFs are food products and beverages that have undergone multiple industrial processing steps and generally contain added flavors, colorants, and other additives. In addition, UPFs are a major source of potentially detrimental compounds, including advanced glycation end products (AGEs), stable molecules generated through non-enzymatic reactions involving reducing sugars and amino residues during complex industrial processing. UPFs and their compounds AGEs may promote the occurrence of obesity and MetS through several and still largely undefined mechanisms. By combining clinical and preclinical data through multi-omic technologies, this project aimed to investigate the role and mechanisms of action of UPFs in the development of obesity and MetS, through the parallel conduction of a clinical phase in a pediatric population and a preclinical phase in a wild-type mouse model. Findings from this study provided new insights into the contribution of UPFs in pediatric obesity and metabolic dysfunction, by integrating clinical observations with mechanistic evidence. Results showed that UPFs not only substantially contribute to pediatric obesity but also promote an unhealthy obesity phenotype characterized by MetS, with a 124% increase in the risk of developing MetS for every 10% increase in daily UPFs intake. The underlying mechanisms ecompassed immune alterations, inflammation, oxidative stress, impaired barrier integrity, mitochondrial metabolism dysfunction, and accumulation in tissues and biological fluids. These results stronlgy support interventions aimed at reducing exposure to UPFs as both a preventive and therapeutic dietary strategy, as well as the exploration of addiotional approaches to mitigate their harmful effects.

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