Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract

• Published in: Histopathology Vol. 68; no. 5; pp. 630 - 640
• Main Author: Feakins, Roger M
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2016; Wiley Subscription Services, Inc
• Subjects: abdominal obesity; Animals; Blood Glucose; Cancer; carcinogenesis; Carcinogens; Disease; Gastrointestinal Diseases - etiology; Gastrointestinal Diseases - pathology; Gastrointestinal Tract - pathology; Growth factors; Humans; Hyperinsulinism; inflammation; Insulin Resistance; Metabolic syndrome; Metabolic Syndrome - complications; Mice; Obesity; Obesity - complications; Obesity, Abdominal; Risk Factors; Triglycerides - blood; metabolic syndrome; carcinogenesis; abdominal obesity; inflammation; obesity
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.12907

Obesity is an increasingly common problem worldwide and a risk factor for a variety of gastrointestinal (GI) 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 GI 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 (MS) 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/MS. 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 GI disease are of variable strength, and the underlying mechanisms are incompletely understood, but it is clear that obesity and MS have a significant, potentially avoidable and often under‐recognized impact on the population burden of GI disease.