Role of the Gastroenterologist in Managing Obesity

John K DiBaise; Amy E Foxx-Orenstein


Expert Rev Gastroenterol Hepatol. 2013;7(5):439-451. 

In This Article

Gastrointestinal Aspects of Obesity Pathogenesis

At its core, obesity results from an imbalance between energy consumed relative to energy expended. Energy intake and expenditure are tightly regulated by the brain, particularly the hypothalamus and brainstem, in a homeostatic mechanism that integrates neural, hormonal and metabolic afferent signals from both the periphery and centrally.[38–40] Although the liver, muscle, adipocytes, pancreatic islets and CNS participate, the GI tract is the first organ affected by nutrient intake. There are a number of factors linking the gut to the pathogenesis of obesity including gut hormones, gut motility and the gut microbiota. Food ingestion results in the release of a number of gut hormones and activates gut motility, gastric and pancreaticobiliary secretion and the digestive and absorptive processes.[41] Meal-related neuronal and humoral signals from the gut are then transmitted to the brain via the blood and through vagal afferent fibers.[38,42] The major gut-derived hormones that influence appetite, satiation and satiety through either central or peripheral actions include ghrelin, cholecystokinin, glucagon-like peptide-1 and peptide YY.[39] Ghrelin is an orexigen that is important in the short-term regulation of food intake. In obesity, an observed postprandial reduction in ghrelin is thought to signal reduced satiety, leading to further food ingestion. In contrast, cholecystokinin is a major mediator of satiety by inhibiting gastric emptying via effects on both fundic relaxation and antral contractility. Glucagon-like peptide-1 is an incretin that modulates glucose control and has similar effects as cholecystokinin on gastric function. Peptide YY is involved in appetite control, the ileal brake and negative feedback to the stomach. Reduced fasting and postprandial levels of peptide YY in obesity have not been consistently demonstrated, however, raising doubts about its central role in the development of obesity.[43] These gut hormones, along with other humoral (e.g., glucagon-like peptide-2, glucose-dependent insulinotropic peptide, oxyntomodulin) and neural signals, act in an integrated fashion to modulate appetite and/or energy expenditure.

As much of the cause of the obesity epidemic involves the overconsumption of food, control of food intake is a major factor in controlling weight.[44] Food intake is associated with important changes in gastric motor function: initial storage of the meal via the vagus nerve–mediated accommodation reflex followed by trituration and emptying of the meal at a rate that optimizes digestive and absorptive efficiency.[41] The nutrient content of a meal also influences the rate of gastric emptying. Although fat plays the major role, the meal volume and total calorie, carbohydrate and protein content of the meal also contribute. Despite the hormonal effects on gastric motility described previously, there have been no changes in gastric emptying consistently seen in obese individuals, and obese individuals (without binge-eating disorder) appear to have normal gastric capacity (i.e., same gastric dimensions as normal-weight individuals).[45] It is likely that much of the conflicting information arises from differences in subject characteristics and the tests used to evaluate gastric function. While the role of altered gastric motor function in the development of obesity remains uncertain, evidence from the dyspeptic population suggests that alterations in gastric motor and/or sensory function are associated with postprandial symptoms that may affect the individual's choice to continue to eat.[46,47] The relevance of this to the obese, non-dyspeptic population requires further study.

There has been an explosion of interest in recent years on the role of the microbes present within our GI tract in health and disease. It has been known for a much longer time that intestinal microbes play an important role in the metabolism of poorly absorbed nutrients. Recent experiments in mice suggest that differences in the composition of gut microbes between obese and lean animals may affect (i.e., enhance in obese mice) energy harvest and storage.[48–50] While intriguing, the studies to date in humans have been conflicting and the relevance of this to humans remains to be determined.[51]