Propionate. Anti-obesity and satiety enhancing factor?

Abstract

Propionate is produced along with acetate and butyrate as a result of fermentative activity of gut microflora on dietary fiber. It has long been known to exhibit hypophagic effects in ruminants, however, its potential physiological roles in non-ruminants as well as humans remained unnoticed over the years. In view of various studies pointing towards the hypophagic as well as hypocholesterolemic effects of propionate in humans, it may act as an important factor in amelioration of obesity, a lifestyle disease arising due to energy imbalance and growing at a startling rate globally. Short chain fatty acids have recently been ascribed as ligands to G-protein coupled receptors (GPRs) 41 and 43. Thus, propionate along with acetate may also be involved in the regulation of adipogenesis and adipokine release mediated via GPRs. The present review summarizes the evidence which collectively raise the possibility of propionate as a dietary factor to depress appetite and combat the obesity epidemic.

Introduction

The human gastrointestinal tract is heavily colonized with trillions of microbes encompassing hundreds of species, endowed with a vast array of hydrolases involved in the fermentation of indigestible carbohydrates that escape digestion while traversing the upper gut (Musso, Gambino, & Cassader, 2010). Microbial fermentation of these plant derived polysaccharides reaching the colon in a substantial amount leads to the production of short chain fatty acids (SCFAs). The bacterial load is highest in the colon with 10¹² cells/ml of the contents where maximal synthesis of SCFAs occurs. In humans, the daily production rate of SCFAs is 300 mmol/day of which only 10 mmol/day is excreted (Hoverstad, 1986). Thus, a major part of SCFAs is being directed towards colonic absorption ranging between 6 and 12 μmol/cm²/h (Cummings, 1981). The major volatile SCFAs produced are acetate, propionate and butyrate in the ratio of 60:25:15 (Macfarlane & Macfarlane, 2003). The SCFAs so produced are metabolized to provide 60–70% of the energy needs of colonic cells (Topping & Clifton, 2001). Of the three SCFAs, butyrate is the major fuel supplied to colonocytes. Acetate is taken up by the liver for cholesterol synthesis while propionate is the major gluconeogenic substrate in ruminants (Bergman, 1990). However, propionate has been shown to inhibit hepatic cholesterol synthesis in humans (Bugaut & Bentejac, 1993). A number of studies indicate that propionate also plays a role in the regulation of food intake in non-ruminants. The recent discovery of SCFAs as ligands to G-protein coupled receptors (GPRs) and their link to adipogenesis also generated mounting evidence for the role of propionate and other SCFAs in the regulation of obesity (Al-Lahham, Peppelenbosch, Roelofsen, Vonk, & Venema, 2010). With obesity reaching pandemic proportions and inclusion of dietary fiber in the diet being advocated, the role of propionate could be highly significant as a preventive measure to check obesity. The present review will focus exclusively on propionate and its potential to act as a satiety inducing and anti-obesity factor in humans.