Increased Propionate Production In The Colon Is Associated With Reduced Appetite Body Weight And Improved Insulin Sensitivity

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Obesity is the greatest public health challenge facing most developed and many developing countries. Obesity is directly related to increased mortality, causing 600 premature deaths in the UK per week. In the current obesity epidemic, using therapeutic foodstuff to tackle obesity is potentially a would be economically viable for industrial partners. Recent epidemiological and experimental studies link the decline in consumption of non digestible carbohydrates (NDC) to the rise in obesity. NDCs are not broken down in the small intestine, but can be fermented by bacteria in the colon, part of the large intestine. Previous studies and our own pilot data shows that increasing the NDC in the diet of animals and humans reduces appetite and body weight and increase insulin sensitivity. Unfortunately, the high doses required to produce these effects are unpalatable and result in side effects, limiting the use of NDC supplements as a treatment for obesity or diabetes. Short chain fatty acids (SCFA) are molecules produced by the fermentation of NDC in the colon and are responsible for the biological effects of NDC. Recently, a receptor has been found that binds SCFAs, and in particular the SCFA propionate. This receptor is found on cells in the large bowel where it stimulates the release appetite-inhibiting hormones, and on fat cells where it acts to decrease the release of free fatty acids. Reducing free fatty acid levels within the body increases the sensitivity of the body to insulin and thus reduces the effect of insulin resistance which is present in type 2 diabetes. Until now, controlling the production of propionate in the colon has been impossible. Both the type of NDC ingested and the gut microbiota of an individual dictate the levels and types of SCFA produced in the colon. Recently, we have developed a novel molecule in which propionate is bound to a carrier molecule. The chemical bond that links proprionate to its carrier molecule cannot be broken down in most parts of the gut. However, in the colon, this chemical bond is broken by the bacteria present there, delivering specific amounts of propionate to the colon. We have shown that supplementing the diet of rats with this proprionate carrier molecule reduces their body weight compared to controls, and that in humans it reduces hunger and food intake. This study will determine the effect of 24 weeks diet supplementation with this propionate carrier molecule on appetite, body weight and insulin sensitivity in obese volunteers. We will test the hypothesis that supplementing the diet with propionate carrier molecule will reduce appetite through gut hormone release and improve insulin sensitivity by reducing the concentration of free fatty acids in circulation. Industry will have an important role in developing products which produce propionate in the colon to reduce appetite and improve insulin sensitivity. In collaboration with Leatherhead Food International we will design foods which can be used to supplement the diet of the general population with proprionate carrier. Demonstrating the link between colonic propionate production and appetite regulation has significant implications for public health given current trends in obesity rates. However, if colonic production of propionate increases satiety, then simply adding any NDC may not be sufficient to increase propionate production to a significant level to impact on satiety. This study will determine if colonic propionate leads to a reduction in appetite and body weight and cause beneficial metabolic change, and will demonstrate proof of principle for using NDC esters to deliver SCFAs to the large intestine. These data will therefore provide valuable information for future studies investigating the effects of SCFAs on appetite regulation and insulin sensitivity. Industry will play an important role in developing products which produce propionate in the colon to reduce appetite and improve insulin sensitivity.