Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract

<jats:p>Obesity is an increasingly common problem worldwide and a risk factor for a variety of gastrointestinal (<jats:styled-content style="fixed-case">GI</jats:styled-content>) diseases, both non‐neoplastic (e.g. gastro‐oesophageal reflux and Barrett's oesophagus) and neoplastic (e.g. oesophageal adenocarcinoma, colorectal carcinoma, and gallbladder cancer). Furthermore, obesity is associated with worse <jats:styled-content style="fixed-case">GI</jats:styled-content> cancer outcomes. Body mass index is a commonly used measure of fat accumulation, although specific patterns such as abdominal/central obesity and visceral fat quantity sometimes predict disease risk more accurately. Metabolic syndrome (<jats:styled-content style="fixed-case">MS</jats:styled-content>) is a related condition characterized by central adiposity and insulin resistance. The reasons for the associations with neoplasia are diverse. Established cancer‐related conditions that have a higher prevalence in overweight subjects include Barrett's oesophagus and gallstones. Preneoplastic lesions such as colorectal adenoma, colorectal serrated lesions and pancreatic intraepithelial neoplasia are also associated with obesity/<jats:styled-content style="fixed-case">MS</jats:styled-content>. At the cellular level, adipocytes can release carcinogens such as adipokines, insulin‐like growth factor, and vascular endothelial growth factor. Inflammatory cells constitute a further potential source of carcinogens; in obese subjects, their numbers are increased systemically and in adipose tissue. Animal studies have contributed additional information. For example, mice with a genetic predisposition to develop colorectal carcinoma given a high‐fat diet have larger and more numerous intestinal adenomas than controls, and there may be demonstrably higher levels of mucosal oncogenic factors. The associations between obesity and <jats:styled-content style="fixed-case">GI</jats:styled-content> disease are of variable strength, and the underlying mechanisms are incompletely understood, but it is clear that obesity and <jats:styled-content style="fixed-case">MS</jats:styled-content> have a significant, potentially avoidable and often under‐recognized impact on the population burden of <jats:styled-content style="fixed-case">GI</jats:styled-content> disease.</jats:p>