The role of propionate in appetite regulation and energy homeostasis

Abstract

Propionate, a product of microbial fermentation, is thought to play a key role in appetite regulation and energy homeostasis. Supplementation with inulin-propionate ester (IPE), which selectively increases colonic propionate production, has previously been reported to reduce energy intake and increase peripheral anorexigenic gut hormone concentrations acutely in humans. Furthermore, long-term IPE-supplementation prevented weight gain and reduced intrahepatocellular lipid content. This thesis aimed to further investigate the effect of colonic propionate on appetite regulation and energy homeostasis in humans. Study 1 investigated the effect of L-rhamnose, a propiogenic non-digestible carbohydrate, on gut transit rates using a dual 13C breath test combined with breath H2. The presented data suggest that L-rhamnose delays gastric emptying rates, increases circulating propionate concentrations and is fermented in the small intestine despite it previously being considered to reach the colon intact. Study 2 investigated the effect of IPE on brain responses to food picture stimuli during an fMRI food picture evaluation task. IPE reduced brain responses to food picture stimuli in the striatum, a brain region involved in reward processing, and reduced their subjective appeal, and reduced energy intake. Study 3 investigated the effect of IPE following a 7-day supplementation period with food products containing IPE (IPE-FP). IPE-FP reduced energy intake. IPE-FP also significantly increased fasting and post-prandial energy expenditure. However, this effect was lost after correcting for lean mass. There was also a reduction in fasting non-esterified fatty acid concentrations following IPE-FP. Finally, study 4 investigated the effect of propionate on liver fat accumulation in two human hepatocyte cell lines. Propionate did not reduce liver fat accumulation in vitro, which suggests the effects observed in vivo may be indirect. The majority of work presented in this thesis supports a role for propionate in energy homeostasis. However, the exact underlying mechanisms remain to be elucidated.