Medical and surgical use of the gut in the treatment of Obesity

Obesity has become a worldwide epidemic that threatens to overwhelm both developed and developing countries. The major burden of obesity to both patients and public health as a whole is the significantly increased morbidity and mortality. It is generally acknowledged that a decrease in physical activity in combination with relative overeating leads to a chronic positive energy balance, thereby causing an increase in body weight. However, other factors that regulate individual susceptibility to obesity in an ‘obesogenic society’ must be involved as well but only a small part has been identified. For example, genetics have been shown to play an important role. Genetic mutations and single nucleotide polymorphisms have been identified that disrupt a highly complex endocrine and neuroendocrine network that regulates energy homeostasis and body weight. The main sites of (inter-)action in this network are white adipose tissue (WAT), the digestive tract and the hypothalamus. The physiology of the gut hormone ghrelin, the peptide obestatin, and the adipokine adiponectin are discussed. Ghrelin is a hormone principally produced in the stomach and primarily identified as a strong growth hormone secretagogue (GHS). Ghrelin circulates in two main isoforms: acylated (AG) and unacylated (UAG) ghrelin. Acylation is crucial for its binding to the known growth hormone receptor type 1a (GHS-R1a). Apart from being a GHS, ghrelin has an important role in energy homeostasis, and in glucose and insulin metabolism. Ghrelin is derived from the polypeptide preproghrelin. The function of a second peptide derived from this prohormone, obestatin, is currently hotly debated. Initially, obestatin was described as a functional antagonist of ghrelin, but subsequent studies were not able to replicate these results. Like ghrelin, adiponectin plays an important role in glucose and insulin homeostasis. Therefore, its connection with ghrelin must be identified. Unfortunately, treatment of obesity is difficult. Currently, bariatric surgery is the most effective treatment when quantified in terms of weight loss. However, it is at least equally important to assess its effectiveness in improving comorbidity. Additionally, any side effects of surgery should be acceptable. The effect of bariatric surgery on quality of life (QoL), and the risk of patients developing gallstones after bariatric surgery are discussed.