Beyond the scale Exploring novel treatment strategies and health impacts of obesity

This thesis explores obesity as a chronic medical condition stemming from an imbalance in energy intake vs energy expenditure and resulting in fat accumulation and increased risks of metabolic disorders. While progress has been made in understanding the aetiology of obesity, mechanisms driving increased energy intake remain partially elusive. Given the growing prevalence of obesity and its associated health hazards, the pursuit of effective preventative and therapeutic measures becomes imperative.
This thesis delves into various drug-based treatments for obesity, such as lorcaserin, which promotes significant weight loss and cardiovascular benefits but was later withdrawn due to concerns about cancer risks. Additionally, we investigate the role of active vitamin D in obesity and its potential impact on brain pathways associated with food intake.
Next, the thesis addresses the intricate connection between obesity, inflammation, and insulin resistance across diverse populations. We show that obesity and insulin resistance are characterised by systemic and tissue-specific inflammation and that bariatric surgery-induced weight loss is associated with reduced inflammation and improved metabolic outcomes. Moreover, we show that metabolic surgery may be effective in patients with some monogenic non-syndromic and syndromic obesity disorders, although lingering concerns persist regarding long-term efficacy.
Finally, the consequences of obesity on the severity of COVID-19 infections are described. We found increased risks of complications without an increase in mortality rates.
In conclusion, this thesis provides insights into potential obesity treatment targets, including modulating inflammatory pathways and vitamin D metabolism. It also underscores the significance of personalised approaches informed by metabolic and genetic factors in managing obesity.