Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity

Obesity is a major global public health issue due to its high morbidity and mortality rates, with its prevalence increasing annually. According to World Health Organization (WHO) estimates, the global population of individuals with obesity has doubled from 1990 to 2022, with over 650 million adults with obesity experiencing metabolic abnormalities such as dyslipidemia, insulin resistance, diabetes, and cardiovascular diseases. Various approaches have been used to treat or prevent obesity including lifestyle interventions, surgery, and pharmacological therapies aimed at reducing energy absorption and increasing energy expenditure. However, these methods do not significantly reduce energy stored in adipose tissues. The conversion of white adipose tissue (WAT) to brown adipose tissue (BAT) presents a promising therapeutic target for obesity treatment. Notably, there is a substantial loss of BAT in individuals with obesity. Conversely, increased BAT is associated with a lower body mass index (BMI), younger age, lower glucose levels, and a decreased incidence of cardiometabolic diseases. Research indicates that BAT formation is modulated by neuro endocrine systems, suggesting a promising therapeutic strategy for obesity prevention and treatment by targeting these systems. In this review, we first discuss the regulation and signaling pathways of neuroendocrine systems involved in energy balance. We then explore the molecular and cellular mechanisms underlying the onset and pathogenesis of obesity and their relationship with neuroendocrine systems. In particular, we summarize the role of the gut-brain axis (GBA) in obesity.