Continuous feeding of a combined high-fat and high-sucrose diet, rather than an individual high-fat or high-sucrose diet, rapidly enhances the glucagon-like peptide-1 secretory response to meal ingestion in diet-induced obese rats

Objectives: Glucagon-like peptide-1 (GLP-1) is secreted by enteroendocrine L-cells in response to nutrient ingestion. To date, GLP-1 secretion in diet-induced obesity is not well characterized. We aimed to examine GLP-1 secretion in response to meal ingestion during the progression of diet-induced obesity and determine whether a combined high-fat and high-sucrose (HFS) diet, an individual high-fat (HiFat), or a high-sucrose (HiSuc) diet affect adaptive changes in the postprandial GLP-1 response. Methods: Rats were fed a control, HiFat diet (30% weight), HiSuc diet (40% weight), or HFS (30% fat and 40% sucrose) diet for 5 wk. Meal tolerance tests were conducted to determine postprandial glucose, insulin, and GLP-1 responses to standard (control) diet ingestion every 2 wk. Results: After 5 wk, body weight gain of the HiFat (2323 +/- 7.8 g; P = 0.021) and HFS groups (228.0 +/- 7.8; P= 0.039), but not the HiSuc group (220.3 +/- 7.9; P= 0.244), were significantly higher than that of the control group (200.7 +/- 5.4 g). In meal tolerance tests after 2 wk, GLP-1 concentration was significantly elevated in the HFS group only (17.2 +/- 2.6 pM; P < 0.001) in response to meal ingestions, but the HiFat group (16.6 +/- 3.7 pM; P= 0.156) had a similar response as the HFS group. After 4 wk, GLP-1 concentrations were similarly elevated at 15 min in the HFS (14.1 +/- 4.4; P= 0.010), HiFat (13.2 +/- 2.0; P < 0.001), and HiSuc (13.0 +/- 3.3; P= 0.016) groups, but the HFS (9.8 +/- 1.0; P= 0.019) and HiFat (8.3 +/- 1.5; P= 0.010) groups also had significant elevation at 30 min. Conclusions: These results demonstrate that the continuous ingestion of excessive fat and sucrose rapidly enhances the GLP-1 secretory response to luminal nutrients, and the HiFat diet may have a potent effect compared with the HiSuc diet on GLP-1 secretory responses. The increment of postprandial GLP-1 and insulin secretion may have a role in normalizing postprandial glycaemia and slowing the establishment of glucose intolerance. (C) 2019 Elsevier Inc. All rights reserved.