The effect of increased colonic propionate production on appetite regulation and energy homeostasis in humans

Abstract

Propionate is a short chain fatty acid produced in the colon via fermentation of undigested foods. Elegant in vitro and in vivo studies have shown that increased production of propionate in the gut can reduce body weight and energy intake, and improve glucose homeostasis. These positive effects have been attributed to increased levels of the gut hormones, PYY and GLP-1, increased energy expenditure and improved beta-cell function. Furthermore, bariatric surgery increases levels of colonic propionate and this likely contributes to the huge weight loss seen with this treatment. Additionally, other short chain fatty acids and the consumption of fermentable carbohydrates to increase levels of short chain fatty acids can delay gastric emptying and affect the central regulation of appetite. Taken together, these findings suggest propionate could have several beneficial health effects in humans.

Inulin-propionate ester was developed to deliver propionate to the colon. Effects of acute delivery of propionate to the colon with a single dose of inulin-propionate ester was investigated in healthy human volunteers on energy intake, subjective ratings of appetite and satiety and plasma glucose and insulin levels. Potential mechanisms for any effects were explored by assessing plasma levels of PYY and GLP-1, gastric emptying using 13C-octanoic acid, energy expenditure using indirect calorimetry, and central effects using fMRI. In addition, encapsulated sodium propionate was used to assess delivery to the small intestine on appetite and glucose and insulin levels.

Acutely increasing colonic levels of propionate significantly reduced energy intake, increased satiety, increased levels of PYY and GLP-1, and reduced anticipatory food behaviour in humans. No effects were observed on gastric emptying, plasma levels of glucose and insulin and energy expenditure. In addition, delivery of propionate to the small intestine did not affect appetite or plasma levels of glucose and insulin.

Colonic propionate significantly reduced energy intake and reduced appetite likely through increasing levels of GLP-1 and PYY and reducing anticipatory food behaviour. In addition, propionate does not affect appetite or glucose and insulin levels via the small intestine. As obesity is a growing epidemic, it is likely that interventions that increase colonic propionate levels could prevent weight gain or drive weight loss by regulating energy homeostasis.