Disentangling the metabolic and psychological wiring in obesity A look beyond the scale

This thesis investigates the biological mechanisms underlying obesity and obesity-related diseases, such as type 2 diabetes and MASLD-MASH, through a systems biology perspective. It emphasizes the multifactorial nature of obesity and its complexities. At its core is the BARIA study, a large longitudinal cohort examining metabolic and psychological changes following bariatric surgery.
A key focus is bile acid metabolism, leveraging a unique dataset of portal bile acids to gain deeper insights into the enterohepatic circulation in individuals with severe obesity. The interaction between portal bile acids and the gut microbiota emerges as critical. Alterations in bile acid profiles after surgery revealing pathways potentially linked to diabetes remission.
The thesis also addresses complications of bariatric surgery, such as post-bariatric hypoglycemia. Using high-throughput sequencing, acylcholines were identified as a novel pathway that may influence glucose metabolism, providing new insights into the condition’s underlying mechanisms.
Psychological dimensions of obesity are explored, including the identification of distinct psychological phenotypes that may impact post-surgery outcomes. Additionally, the role of self-compassion is highlighted as a potential factor in enhancing patients' overall well-being.
Finally, the gut microbiota's role is underscored by the discovery of microbiota-generated ethanol in the portal vein, correlating with MASLD-MASH markers and suggesting a significant role in disease pathogenesis.
In summary, this research integrates microbiome, metabolic, and psychological factors, advancing understanding of the complexity of obesity and metabolic diseases while paving the way for innovative, personalized treatments.