Background  Roux‐en‐Y gastric bypass (RYGB) surgery is very effective in reducing excess body weight and improving glucose homeostasis in obese subjects. Changes in the pattern of gut hormone secretion are thought to play a major role, but the mechanisms leading to both changed hormone secretion and beneficial effects remain unclear. Specifically, it is not clear whether changes in the number of hormone‐secreting enteroendocrine cells, or changes in the releasing stimuli, or both, are important.

Methods  We estimated numbers of enteroendocrine cells after immunohistochemical staining in fixed tissue samples from rats at 10–11 months after RYGB.

Key Results  Numbers of glucagon‐like peptide‐1 (GLP‐1) (L‐cells, co‐expressing peptide YY (PYY)), cholecystokinin (CCK), neurotensin, and 5‐HT‐immunoreactive cells were significantly increased in the Roux and common limbs, but not the biliopancreatic limb in RYGB rats compared with sham‐operated, obese rats fed high‐fat diet, and chow‐fed controls. This increase was mostly accounted for by general hyperplasia of all intestinal wall layers of the nutrient‐perfused Roux and common limbs, and less to increased density of expression. The number of ghrelin cells in the bypassed stomach was not different among the three groups.

Conclusions & Inferences  The findings suggest that the number of enteroendocrine cells increases passively as the gut adapts, and that the increased total number of L‐ and I‐cells is likely to contribute to the higher circulating levels of GLP‐1, PYY, and CCK, potentially leading to suppression of food intake and stimulation of insulin secretion. Whether changes in releasing stimuli also contribute to altered circulating levels will have to be determined in future studies.