Background:
Previous research has demonstrated that acute propionate supplementation in humans can have favourable effects on energy metabolism by raising energy expenditure and lipid oxidation. Moreover, acute propionate supplementation in humans has shown to affect subjective appetite by increasing nausea and triggering the release of the anorectic hormone glucagon-like peptide 1 (GLP-1). Studies investigating the acute effects of propionate administration on glucose homeostasis in humans report conflicting outcomes. However, previous research has generally only investigated the acute impact of propionate supplementation in the overnight fasted state and for relatively short observation periods (<180 min).It is, therefore, presently unknown how raised bioavailability of gut-derived propionate modulates energy metabolism during physical activity and in the postprandial state. Consequently, the aim of the present trial is to investigate the acute effect of sodium propionate supplementation on energy expenditure, substrate oxidation, appetite response and glucose homeostasis in three different energy states (overnight fasted, sub-maximal exercise and post-prandial) and over longer time-periods. Moreover, NMR (nuclear magnetic resonance) spectroscopy was used to investigate changes in serum metabolite phenotype after sodium propionate ingestion.
Methodology:

The thesis is comprised of three separate randomized controlled double-blind cross-over studies (overnight fasted, submaximal exercise, and postprandial). In each study, following an overnight fast, tablets containing either sodium propionate or sodium chloride (Control) were first administered over 180 min.

Overnight Fasted study: 19 volunteers (11 males and 8 females; age: 34.6  4.1 years; BMI (body mass index): 23.1  0.7 kg/m2) completed the two study visits after an overnight fast. The study extended over a total period of 360 min while volunteers remained fasted for the duration of the study.

Sub-maximal exercise study: 19 volunteers (14 males and 5 females; age: 42.7  3.5 years; BMI: 24.5  0.7 kg/m2) completed a maximal exercise test visit and two study visits. The study extended over a total period of 240 min. At time-point 180 min, participants exercised at 40% of VO2 max for 60 min.

Post-prandial study: 19 volunteers (12 males and 7 females; age: 45.0  3.5 years; BMI: 24.8  0.8 kg/m2) completed two study visits. The study extended over a total period of 300 min. At time-point 180 min, a mixed calorie liquid meal (Ensure Original Vanilla Nutrition Shake: 72.7 g carbohydrate, 13.6 g fat and 20.5 g protein; 500 kcal) was provided to volunteers.

Energy expenditure and substrate oxidation were measured throughout these visits using indirect calorimetry. Participants were asked to complete 100mm visual analogue scales (VAS) that assessed subjective appetite (hunger, thirst and nausea) throughout these visits. Insulin resistance and insulin sensitivity were assessed via HOMA-IR and Matsuda Index respectively. The oral disposition index (ODI) was used to assess β-cell function. In the post-prandial trial, GLP-1 release was measured, and 1H-NMR spectroscopy was used to analyse serum metabolite profile associated with propionate supplementation.

Results:

Propionate supplementation increased energy expenditure in the overnight fasted state, which was mainly observed within the first 180 min of ingestion, and in the post-prandial state. A consistent increase in lipid oxidation was found in the overnight fasted state, however, these effects were not observed during submaximal exercise or in the post-prandial state. A decrease in carbohydrate (CHO) oxidation was also found in the overnight fasted state. Propionate ingestion increased subjective nausea in the overnight fasted and post-prandial states and increased subjective thirst during submaximal exercise. However, no effect on subjective hunger was found was found in the three different energy states. GLP-1 secretion was significantly increased in the overnight fasted state, however, insulin sensitivity and β-cell function were unaffected with propionate ingestion. In the overnight fasted state, low density lipoprotein (LDL)/ very low-density lipoprotein (VLDL), lactate and methanol were upregulated and 3-hydroxybutyrate and lysine were supressed following propionate supplementation. LDL/VLDL, lactate and alanine were upregulated following propionate supplementation in the postprandial state.

Conclusion:
This thesis is the first to demonstrate that acute oral sodium propionate supplementation in healthy human volunteers can have favourable effects on energy metabolism in different energy states. Should these effects be replicated over longer time periods would suggest that increasing systemic levels of gut-derived propionate appears would be a promising strategy to improve long term energy balance and body weight management.