Comparison between nutritional, pharmacological, and surgical treatment of obesity on circulating levels of hormones regulating hunger and food-seeking

Obesity is a complex and multifactorial disease, leading to a range of serious health complications, including an increased risk of cardiovascular diseases, diabetes, some types of cancer, respiratory issues, and overall reduced life expectancy. It is the result of a chronic energy imbalance between energy intake and expenditure. The rapid increase in obesity over the past 30 years is primarily attributed to an obesogenic environment, characterized by high-energy density diets, larger portion sizes, low physical activity, sedentary lifestyles, and eating disorders. These behavioral and environmental factors lead to alterations in adipose tissue structure (hypertrophy and hyperplasia of adipocytes, as well as inflammation) and in the secretion of hormones from the adipose tissue (leptin, adiponectin) and gastrointestinal cells (GLP-1, PYY, CKK), which in the end impair the satiety-hunger sensation. Targeting these entero-hormones and their receptors has become a primary therapeutic strategy for the pharmacological management of obesity. The present study aims to better understand the role of the novel orexigenic hormone INSL5 as a potential therapeutic target, as well as other well-known entero-hormones (such as GLP1). In this research we compared the effect of three different types of obesity treatments (pre- and post-Bariatric surgery, pre- and post-GLP1-Receptor Agonist and pre- and post- diet) on the serum concentration of INSL5 and inflammatory biomarker MCP1, to obtain more insights about the inflammatory profile of the patients. Our results show that INSL5 concentrations decreased only in the post-bariatric surgery group, whereas all post-treatment groups exhibited lower MCP1 concentrations. However, the mechanisms regulating the synthesis and secretion of INSL5 remain poorly understood and further investigations are required to determine whether the observed decrease in INSL5 plays a causal role in the clinical benefits after bariatric surgery or simply represent a secondary effect of metabolic adaptations induced by the procedure.