Gastric emptying in humans; carbohydrate ingestion, gastrointestinal hormones and genetic variation

The prevalence of overweight and obesity continues to rise substantially across the world. It is the leading preventable cause of death worldwide and is associated with a large number of comorbidities that present a perpetual burden on healthcare costs. Much of the recent work to understand and address the problem of obesity has focused on the role of gastrointestinal hormones on the regulation of appetite, satiety, and food intake, and how interventions such as physical activity and exercise can affect the secretion of these hormones. However, the gastrointestinal system and the role of gastric emptying are often overlooked. The aim of this thesis was to enhance understanding of the physiology and regulation of gastric emptying and its interactions with carbohydrates. This will help in the development of novel non-pharmacological dietary interventions or foods that can modulate appetite and energy intake. A series of studies on human volunteers are presented in this thesis. Firstly, the gastric emptying rate of different 6% simple sugar solutions (water control, fructose, glucose, sucrose, 50:50 fructose and glucose) and gut hormone responses of circulating acylated ghrelin, active glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic polypeptide (GIP) and insulin were investigated. Hepatic metabolism and function in response to the different simple sugar solutions were also examined. The time of maximal gastric emptying rate (Tlag) differed significantly between between sucrose and glucose solutions. Differences in insulin and GIP responses between fructose containing solutions and glucose only solutions were also seen. No differences in hepatic metabolism measures or function were observed following the intake of 36 g of the various test sugars. However, lactate production was significantly greater for fructose containing solutions. Following on from these results, the effect of increased dietary fructose intake on gastric emptying rate of glucose and fructose was investigated. Three days supplementation with 120g/d fructose resulted in acceleration of gastric emptying rate of a fructose but not a glucose solution. No significant differences in the circulating concentration of gastrointestinal hormones, but subtle differences in responses over time were suggested which may explain the specific monosaccharide adaptations of gastric emptying. Further work is required to confirm this and to investigate the longevity and reversibility of the gastrointestinal adaptation and the mechanism involved. Lastly, several tagging single nucleotide polymorphisms (SNP) of the GLP-1 receptor gene were associated with gastric emptying rate. Further work is required on the regions identified to pinpoint the exact SNP or SNPs responsible

The effect of glucose or fructose added to a semi-solid meal on gastric emptying rate, appetite and blood biochemistry

The ingestion of fructose is of interest due to previously reported differences in gastrointestinal, appetite, and metabolic effects when compared to glucose ingestion when ingested in liquid solution. The aim of this study was to examine these variables when fructose and glucose are added to a semi-solid meal. Seven healthy male participants completed three experimental trials involving the ingestion of 300 mL of semi-skimmed milk mixed with 40 g of instant porridge mix (CON) and with the addition of either 40 g of glucose (GLU) or fructose (FRU). Subjective feelings of appetite were assessed for 2 h after ingestion with blood samples collected at regular intervals. Gastric emptying rate was assessed using the 13C breath test method. Half emptying time was not different between trials (CON = 159 ± 51 min; GLU = 197 ± 46 min; FRU = 198 ± 67 min: P = 0.117). No differences were observed for any subjective measurements of appetite (P > 0.05) while blood glucose was elevated (P < 0.05) 20 min after ingestion on both GLU and FRU with this tending to be higher on GLU than FRU. FRU resulted in greater (P < 0.05) blood lactate concentrations than on the other trials. The results of this study demonstrate that gastric emptying rate of glucose and fructose is similar when ingested in a semi-solid meal. In addition, there is little difference in appetite response between these sugars, however, there are some differences in metabolic response which deserve further study

A Comparison of Intermittent and Continuous Exercise Bouts at Different Intensities on Appetite and Postprandial Metabolic Responses in Healthy Men

Exercise intensity affects many potential postprandial responses, but there is limited information on the influence of exercise modality. Therefore, the aim of this study was to investigate if the nature of exercise at two different intensities would affect gastric emptying rate (GER), appetite and metabolic responses following ingestion of a semi-solid meal. Twelve healthy men completed, in a random order, four 60-min cycles at 60% VO2peak (MOD), 40% VO2peak (LOW) and in a continuous (CON) or intermittent (INT) manner. INT consisted of 20 × 1-min exercise bouts with 2-min rest breaks. INT and CON were matched for total work output at each intensity. GER of the post-exercise meal was measured for 2 h using the 13C-breath method. Blood glucose, substrate utilisation and appetite ratings were measured at regular intervals throughout all trials and 24-h energy intake (EI) post-trials was assessed. GER-Delta over Baseline (DOB) was lower (p 0.05). 24-h post-trial EI was similar between LOW-CON vs. LOW-INT (p > 0.05), although MOD-INT vs. MOD-CON 3500 ± 1419 vs. 2556 ± 989 kCal: p < 0.001 was elevated. In summary, MOD-INT exercise delays GER without stimulating perceived appetite in the 2 h period after meal ingestion, although EI was greater in the 24-h post-trial

The effect of brisk walking in the fasted versus fed state on metabolic responses, gastrointestinal function, and appetite in healthy men

Objective To investigate the effect of brisk walking in the fasted versus fed state on gastric emptying rate (GER), metabolic responses and appetite hormone responses. Subjects/methods Twelve healthy men completed two 45 min treadmill walks, fasted (FASTED) and followed consumption of a standardised breakfast (FED). GER of a standardised lunch was subsequently measured for 2 h using the 13C-breath test method. Blood samples were collected at baseline, post-breakfast period, pre-exercise, immediately post exercise, pre-lunch then every 30 min following lunch for 2 h. Circulating concentrations of acylated ghrelin (GHR), glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), pancreatic polypeptide (PP), glucose, insulin, triglycerides, non-esterified fatty acids (NEFA) and cholesterol were measured. Subjective feelings of appetite were assessed at 15 min intervals throughout. Substrate utilisation was measured every 30 min, and continuously throughout exercise by indirect calorimetry. Results No differences were observed for GER T½ (FASTED 89 ± 22 vs. FED 89 ± 24 min, P = 0.868) nor Tlag (FASTED 55 ± 15 vs. FED 54 ± 14 min, P = 0.704). NEFA concentrations were higher in FASTED at pre-exercise, post exercise and 30 min post exercise (pre-lunch) (all P < 0.05) but no differences were observed for glucose, cholesterol or triglycerides. Carbohydrate oxidation was greater at all time-points during FED exercise (all P < 0.05). Minimal changes in appetite were observed post lunch ingestion with no differences in PYY or GHR observed between trials. GLP-1 concentrations were greater in FED post-breakfast and pre-exercise (P < 0.05), though no differences were observed after lunch. A greater concentration of PP was observed in FED from pre-exercise to 30 min post lunch consumption (all P < 0.05). Insulin concentrations were higher in FED pre-exercise but higher in FASTED 1.5 h post lunch (P < 0.05). Conclusion These findings suggest that gastrointestinal function, hunger and appetite regulatory hormones are not sensitive to low-intensity bouts of physical activity and holds positive implications for weight management practices

A pilot study investigating the influence of glucagon-like peptide-1 receptor single nucleotide polymorphisms on gastric emptying rate in Caucasian men

Gastric emptying rate in humans is subject to large individual variability, but previous research on the influence of genetics is scarce. Variation in the glucagon-like peptide-1 receptor (GLP1R) gene is a plausible candidate gene to partially explain the high variance. This study aimed to investigate the influence of genetic variation in the GLP1R gene on gastric emptying rate of a glucose solution in humans. Forty eight healthy Caucasian males took part in this investigation. Gastric emptying rate of a 6% glucose solution was assessed using the 13C breath test method and a venous blood sample was obtained from each participant. Participants were genotyped for twenty-seven Tag single nucleotide polymorphisms (SNPs) in the GLP1R locus using Sequenom MassARRAY iPLEX GOLD analysis and MALDI-TOF mass spectrometry. The time at which maximal emptying rate occurred (Tlag) was faster in participants with the CC genotype than in TT and TC genotypes for SNP rs742764: (Median (quartiles) CC, 35 (30-36) min vs. TT, 43 (39-46) min and TC, 41 (39-45) min; P < 0.01). Tlag was also slower in participants with the AA genotype compared to the TT and TA genotypes for SNP rs2254336: (AA, 43 (39-49) min vs. TT, 36 (34-41) min and TA, 39 (35-42) min; P < 0.05). Analysis by phenotype also showed differences in half-emptying time (T½) and Tlag for SNPs rs9283907, rs2268657 and rs2254336. Several neighbouring Tag SNPs within the GLP1R gene were found to be associated with gastric emptying rate, and should be further investigated

A comparison of intermittent and continuous exercise bouts at different intensities on appetite and postprandial metabolic responses in healthy men

Exercise intensity affects many potential postprandial responses, but there is limited information on the influence of exercise modality. Therefore, the aim of this study was to investigate if the nature of exercise at two different intensities would affect gastric emptying rate (GER), appetite and metabolic responses following ingestion of a semi-solid meal. Twelve healthy men completed, in a random order, four 60-min cycles at 60% VO2peak (MOD), 40% VO2peak (LOW) and in a continuous (CON) or intermittent (INT) manner. INT consisted of 20 × 1-min exercise bouts with 2-min rest breaks. INT and CON were matched for total work output at each intensity. GER of the post-exercise meal was measured for 2 h using the 13C-breath method. Blood glucose, substrate utilisation and appetite ratings were measured at regular intervals throughout all trials and 24-h energy intake (EI) post-trials was assessed. GER-Delta over Baseline (DOB) was lower (p 0.05). 24-h post-trial EI was similar between LOW-CON vs. LOW-INT (p > 0.05), although MOD-INT vs. MOD-CON 3500 ± 1419 vs. 2556 ± 989 kCal: p < 0.001 was elevated. In summary, MOD-INT exercise delays GER without stimulating perceived appetite in the 2 h period after meal ingestion, although EI was greater in the 24-h post-trial