Endocrine Abstracts (2015) 38 S10.3 | DOI: 10.1530/endoabs.38.S10.3

Short chain fatty acids in the regulation of energy homeostasis

Gary Frost

Imperial College London, London, UK.

In recent years, there has been a renewed interest in the role of dietary fibre in obesity management. Much of this interest stems from animal and human studies that suggest increased intake of fermentable fibre can improve body composition.

A growing number of reports have demonstrated that the principal products of colonic fermentation of dietary fibre, short chain fatty acids (SCFAs), contribute to energy homeostasis via effects on cellular metabolic pathways and receptor mediated mechanisms. In particular, over the past decade it has been identified that a widespread receptor system exists for SCFAs. These G protein-coupled receptors, free fatty acid receptor 2 (FFAR2) and 3 (FFAR3) are expressed in numerous tissues, including the gut epithelium, adipose tissue and liver. Investigations using FFAR2- or FFAR3-deficient mice suggest that SCFA-mediated stimulation of these receptors at different tissue sites modulates metabolic processes that control energy intake, utilization and expenditure.

The importance of SCFAs to metabolism has been further emphasised in studies where germ-free mice have received gut microbiota transplants. These investigations highlight that the transfer of gut microbiota compositions that produce different levels of SCFAs in the colon influence body weight gain and adiposity. Increasing colonic SCFAs is therefore an attractive target to improve metabolic health in humans. However, translating the positive outcomes observed in animal studies into humans remains a major challenge due to the difficulty in reliably increasing SCFA production in the human colon. Our group in partnership with the University of Glasgow have developed a method to deliver SCFA to the colon orally. We have demonstrated the potential of SCFA to effect body weight over a 6 month period using this technology. However, the mechanism which underlie this observation remains unclear, potential possibilities will be discussed in this lecture.

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