Responses of gut and pancreatic hormones, bile acids, and fibroblast growth factor-21 differ to glucose, protein, and fat ingestion after gastric bypass surgery

Abstract

Postprandial gut hormone responses change after Roux-en-Y gastric bypass (RYGB), but little is known about the importance of the different macronutrients for this. We investigate the impact of glucose, protein and fat (with and without pancreas lipase inhibition) on plasma responses of gut and pancreas hormones, bile acids and FGF-21 after Roux-en-Y gastric bypass (RYGB) and in matched non-operated control subjects. In single-blinded, randomized, cross-over study ten RYGB operated and eight healthy weight-matched control subjects were administered four different 4-hour isocaloric (200 kcal) liquid meal-tests containing >90E% of either glucose, protein (whey protein) or fat (butter with and without orlistat®). The primary outcome was GLP-1 secretion (area under the curve above baseline). Secondary outcomes included responses of PYY, GIP, CCK, glicentin, neurotensin, insulin, glucagon, bile acids and FGF 21. In the RYGB group the responses of GLP-1, GIP, glicentin, FGF-21 and C-peptide were increased after glucose compared with the other meals. The neurotensin and bile acids responses were greater after fat, while the glucagon and CCK responses were greater after protein ingestion. Furthermore, compared with control subjects, RYGB subjects had greater responses of total PYY after glucose, glucagon after glucose and fat, glicentin after glucose and protein, and GLP-1 and neurotensin after all meals, while GIP and CCK responses were lower after fat. Orlistat® reduced all hormone responses to fat ingestion. In conclusion, after RYGB glucose is a more potent stimulator of most gut hormones, especially for the marked increased secretion of GLP-1 compared with fat and protein.