Investigating Optimal Propionate Delivery to the Colon Using Stable Isotope Labeling

Summary

Obesity, with its associated co-morbidities, is a major public health challenge. It is estimated that by 2050, 60% of men and 50% of women will be clinically obese. Obesity is associated with increased risk of developing diabetes, cardiovascular disease, and certain cancers. The increasing epidemic of obesity has necessitated the study of the complex mechanisms underlying energy homeostasis. Food intake, energy balance and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including glucagon-like peptide-1 (GLP-1) and peptide YY3-36 (PYY), have been shown to play an important role in regulating short-term food intake. Peripheral administration of PYY or GLP-1 enhances satiety and reduces food intake in animals and man. PYY, GLP-1 along with a host of other hormones are produced by the gut in response to nutrient availability in different regions of the gut and provide an exquisite mechanism of nutrient sensing in response to dietary intake. These hormones therefore represent potential targets in the development of novel anti-obesity treatments. A novel and attractive strategy to induce appetite regulation is the enrichment of foods with components that stimulate the release of GLP-1 and PYY. The short chain fatty acids (SCFA) produced by microbial fermentation of dietary fibre in the colon have been shown to stimulate the release of PYY and GLP-1 from rodent enteroendocrine L cells, via stimulation of the G-protein coupled free fatty acid receptors (FFAR) on colonic L cells. Of the SCFAs produced by colonic fermentation of dietary fibre, propionate has the highest affinity for FFAR 2. Furthermore, propionate is an end product of bacterial metabolism, and thus, unlike acetate, does not undergo conversion to other SCFAs. Increasing colonic propionate is therefore an attractive target for appetite modulation.

We have developed a novel delivery system for delivering propionate to the right site in the colon and we now wish to optimise the delivery of propionate to the colon in man using stable isotope labelling methods.

Conditions

• Optimum Propionate Delivery to the Large Intestine

Interventions

DIETARY_SUPPLEMENT

Inulin

DIETARY_SUPPLEMENT

2.5 g of propionate

This system delivers approximately 2.5 g of propionate to the colon in a 10g dose.

DIETARY_SUPPLEMENT

5 g of propionate

This delivers approximately 5g of propionate to the colon per 10g dose

Sponsors & Collaborators

• Biotechnology and Biological Sciences Research Council

  collaborator OTHER

• University of Glasgow

  collaborator OTHER

• Scottish Universities Environmental Research Centre

  lead OTHER

Principal Investigators

• Douglas Morrison, PhD · University of Glasgow

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

21 Years

Max Age

65 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-08-31

Primary Completion

2015-08-31

Completion

2015-12-31

Countries

• United Kingdom

Study Locations