Abstract
The obesity epidemic is driving interest in identifying strategies that enhance appetite control by altering the secretion of hormones that regulate satiety and food intake. An appropriate nutrient stimulus, such as a meal or oral nutrient solution, is needed to elicit the secretion of satiety hormones in order to evaluate the impact of dietary and other interventions. Our objective was to compare the effects of oral glucose vs. mixed nutrients on plasma concentrations of glucose and appetite-regulating hormones to determine the most appropriate oral nutrient challenge to trigger robust hormone secretion. A 120 min oral glucose tolerance test (OGTT) was compared with two meal tolerance tests (MTT) of differing formulation to evaluate glucose and satiety hormone responses. Following overnight feed deprivation, male Sprague-Dawley rats were given one of three oral gavages with equal carbohydrate content (2 g CHO/kg) in the form of: (1) Dextrose, (2) Ensure®, or (3) Mixed Meal. A fourth group was given saline as a control. Blood was collected via tail snip and analyzed for glucose, insulin, GLP-1, GIP, PYY, amylin, leptin, and ghrelin. Dextrose resulted in the highest blood glucose at T15 (P = 0.014), while the mixed meal was significantly higher than saline from T30-T120 (P < 0.05). Insulin was higher at T15 with dextrose compared to saline (P = 0.031) and Ensure® (P = 0.033). GLP-1 tAUC was significantly higher with dextrose compared to mixed meal (P = 0.04) while GIP tAUC was higher with dextrose and mixed meal compared to saline (P < 0.05). Changes in tAUC for insulin, amylin, leptin, ghrelin, and PYY did not reach significance. Based on these findings, dextrose appears to provide a robust acute glycemic and hormone response and is therefore likely an appropriate oral solution to reproducibly test the impact of various dietary, surgical, or pharmacological interventions on glucose and satiety hormone response.
Highlights
Substantial resources have been dedicated to the treatment of obesity and related comorbidities including diabetes, hypertension, and cardiovascular disease [1]
It was anticipated that the secretion of one of the primary satiety hormones of interest, glucagon-like peptide-1 (GLP-1), would be greatest following the mixed meal due to the combined macronutrient composition of the treatment [13] and that other related hormones, such as the other incretin glucose-dependent insulinotropic peptide (GIP) or peptide YY (PYY) which is co-expressed with GLP-1 in intestinal L cells [18], would react
We chose to compare a mixed meal treatment that was prepared in-house with the commercially available liquid meal replacement, Ensure R. We found that both the dextrose and mixed meal treatments elicited a greater blood glucose response compared to saline
Summary
Substantial resources have been dedicated to the treatment of obesity and related comorbidities including diabetes, hypertension, and cardiovascular disease [1]. Hormone Response to Glucose vs Mixed-Meal includes leptin, insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin among others [3]. Exposure to either an oral glucose tolerance test (OGTT) or a meal tolerance test (MTT) is a common protocol used to demonstrate changes in the release of satiety hormones in response to an acute stimulus such as a drug or nutrient or following longer term interventions to assess the effects of treatments such as bariatric surgery or dietary change on satiety hormones. Studies showing substantial changes in the release of appetite-regulating hormones following bariatric surgery have helped to identify one of several potential mechanisms by which this surgery enhances weight loss and leads to diabetes resolution [6, 7]
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