Gastrointestinal surgery and gut hormones

Abstract

Purpose of review Surgical treatment of obesity remains by far the most effective means of achieving weight loss, and in addition leads to normalised glucose tolerance in patients with type 2 diabetes mellitus (T2DM). Bariatric surgical procedures have recently been shown to effect changes in the secretion of gastro-intestinal hormones involved in energy regulation and intermediary metabolism that may contribute to appetite reduction, weight loss and remission of T2DM. Recent findings Ghrelin is released from the stomach in the pre-prandial state and stimulates food intake. Weight loss through dietary restraint elevates the low circulating levels of ghrelin in obese subjects, but following Roux-en-Y gastric bypass surgery (RYGB), obese subjects were shown to have suppressed levels of ghrelin. Subsequent prospective studies, however, have found inconsistent ghrelin responses following RYGB. Peptide YY (PYY) is expressed in the ileum, released in response to the ingestion of food and acts centrally to inhibit food intake. Recent studies have shown that PYY levels are reduced in obesity although obese subjects remain sensitive to exogenous PYY. Following RYGB, PYY release is exaggerated, an effect that should inhibit subsequent meal size. Glucagon-like peptide 1 (GLP-1), released from the same cells as PYY, shows a pronounced post-prandial elevation after RYGB that may be responsible for an enhanced early insulin release and contribute to the normalisation of glucose homeostasis. Summary The pleiotropic endocrine effects of RYGB that favor weight loss present strong circumstantial evidence for a humoral effect of RYGB on appetite and food intake. Mimicking the effects of RYGB on the entero-hypothalamic axis has become an attractive goal for pharmacotherapy.