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Propionate – your ally against overeating?

When you eat food, it results in a complex interplay between the food’s components, our gut microbiome, and our gut and brain’s response. It turns out that a type of fatty acid resulting from this process may help reduce appetite.

Study under review: Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods

Introduction

In NERD #6, Margaret Leitch discussed the neurobiology of eating behavior. Basically, the food industry is great at bringing out the best in food, making it “hyper-palatable” to consumers. Chronic exposure to hyper-palatable food can lead to changes in brain chemistry, similar to changes observed with drug use. People literally become addicted to these foods and can experience withdrawal symptoms when they stop eating them.

Our liking of food and the reward system involved with hyper-palatability is believed to involve a combination of brain regions[1] (shown in Figure 1) involved in the regulation of emotion, decision making, and impulse control: the hypothalamus, nucleus accumbens, amygdala, anterior insula, caudate nucleus, and orbitofrontal cortex (OFC). These regions react in response to numerous gut hormones[2] produced in the stomach, small intestine, pancreas, and colon, as well as visual and olfactory (smell) cues.

For instance, glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) are secreted by cells within the ileum (end portion of the small intestine) and within the colon in response to food, especially carbohydrates and fats. Infusion of GLP-1 reduces energy intake[3] in both lean and overweight individuals, an effect believed to be caused at least partly by GLP-1 affecting[4] the hypothalamus and caudate brain regions. Infusion of PYY has also been shown to reduce food intake[5] and hunger in lean and obese people.

While there has been a tremendous amount of research investigating how these and other gut hormones impact the brain’s regulation of appetite, emerging research suggests that not all potential brain modulators are made by us. One massive part of the digestive system that may influence satiety[6] is the gut microbiome. Evidence in rodents suggests that resistant[7] starch[8] (a type of fermentable fiber) supplementation influences appetite through effects on gene expression and the brain. Similar findings have also been observed with the fibers beta-glucan[9] and inulin[10].

Figure 1: Example of hedonic circuits in the sagittal rodent brain

References: Berridge, K. Physiol Behav. 2009 Jul. and Smith, K, et al. Behav Brain Res. 2009 Jan.

What the above fibers all have in common is that they are metabolized by the gut microbiome, producing short-chain fatty acids (SCFAs) as a byproduct. The primary SCFAs are acetate, propionate, and butyrate. Preliminary animal research[11] suggests that circulating acetate crosses the blood-brain barrier to directly influence appetite regulation centers. Additionally, the SCFAs have been shown to promote the release[12] of several gut hormones that promote satiety through their influence on the brain.

Recently, human research[13] has shown that delivering propionate directly to the colon increases the secretion of PYY and GLP-1 and reduces energy intake at a buffet meal. It also significantly reduced weight gain over a 24-week supplementation period. This was done with an inulin-propionate ester (IPE), whereby propionate is bonded by an ester linkage to inulin, a carrier molecule. The ester linkage is broken down by the gut bacteria, which results in the delivery of propionate directly to the colon.

The study under review was a follow-up to the above IPE research. It sought to examine the effect of an acute increase in colonic propionate production on energy intake and brain regions involved with reward processing and eating.

Satiety and food reward are an intricate dance between numerous gut hormones, the gut microbiome, and the brain. Previous research has shown that increasing the amount of the short-chain fatty acid propionate in the human colon reduces weight and appetite. The current study sought to examine how increasing propionate influences energy intake and brain activity.

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