Research reportGut hormone release and appetite regulation in healthy non-obese participants following oligofructose intake. A dose-escalation study☆
Highlights
► Assessment of stepwise dose increases of oligofructose on appetite and gut hormones. ► Oligofructose dose-dependently elevated plasma PYY and suppressed PP and ghrelin. ► Doses of oligofructose ⩾35 g/day significantly changed postprandial plasma PYY and PP. ► Doses ⩾25 g/day reduced hunger scores in the home environment, but not in acute tests. ► Oligofructose did not affect energy intake in this study.
Introduction
Obesity is a major public health problem worldwide and the prevention of weight gain in adults is a major public health target. The rapid increase in obesity tracks with change in food processing to more energy dense food (Astrup, Dyerberg, Selleck, & Stender, 2008). A major determinant of energy density is dietary carbohydrate and specifically dietary fibre (Grunwald, Seagle, Peters, & Hill, 2001). In the recent years, fermentable dietary fibres have attracted more attention. Oligofructose is a non-digestible short-chain fructan derived from inulin and has recently been recognised as a dietary fibre (Cummings, Mann, Nishida, & Vorster, 2009). Several studies have reported that oligofructose and an inulin/oligofructose mixture potently suppress food intake, reduce weight gain, and improve body composition in rodent models (Cani et al., 2005, Delmee et al., 2006, Delzenne et al., 2005, Ten Bruggencate, 2010). The appetite suppressing properties of oligofructose have been linked to an elevation of portal concentrations of the anorectic gut hormones peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP-1) and suppression of the orexigenic hormone, ghrelin (Cani et al., 2004, Cani et al., 2005, Parnell and Reimer, 2012). Interestingly, in a dose–response study in rats, an inulin/oligofructose mixture (0, 10, and 20% w/w) induced a dose-dependent increase in caecal proglucagon and PYY mRNA and plasma active GLP-1 concentrations in rats (Parnell & Reimer, 2012).
Evidence from ex vivo, animal, and human studies supports the notion that sensing of luminal short-chain fatty acids (SCFAs), products of bacterial fermentation of non-digestible carbohydrates, is involved in the release of PYY and GLP-1 from enteroendocrine L-cells (Cherbut et al., 1998, Freeland and Wolever, 2010, Fu-Cheng et al., 1995, Lin et al., 2012, Longo et al., 1991, Plaisancie et al., 1996, Tolhurst et al., 2012). Increasing the intake of fermentable fibres may be a means of achieving a more favourable gut hormone profile in terms of appetite control, through an increase in SCFA by colonic fermentation.
To date few studies have investigated the effect of oligofructose on appetite and appetite regulating hormones in humans with varied results. Oligofructose supplementation at 16–21 g/day improved appetite regulation, increased postprandial PYY and/or GLP-1 concentrations, and reduced energy intake in adults (Cani and Joly et al., 2006, Cani et al., 2009, Parnell and Reimer, 2009, Verhoef et al., 2011) and 8 g/day attenuated the increase in BMI and total body fat mass in children (Abrams, Griffin, Hawthorne, & Ellis, 2007). In a study evaluating the effects of 10 and 16 g oligofructose per day in normal weight participants, Verhoef et al. (2011) reported that 16 g oligofructose may be the lowest effective dose to elevate PYY3-36 and reduce energy intake. However, to date no one has sought to establish the optimal dose of oligofructose in humans with respect to appetite regulation by testing a wide range of doses of oligofructose. The objective of this study was to investigate the dose of oligofructose needed to achieve a consistent change in subjective appetite without producing adverse gastrointestinal side effects. Secondary outcomes were appetite regulating hormones and energy intake. This data could then be used to explore the potential of oligofructose to decrease weight gain in adults.
Section snippets
Participants
This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures were approved by the University of Surrey’s Ethics Committee (project registration number: EC/2007/67/FHMS). Written informed consent was obtained from all participants.
All participants were recruited from the staff and student body at the University of Surrey by local advertisement and required to be healthy, non-smokers, and free from medication (with the exception of minor
Data collected within the home environment
To have a holistic view of the impact of the oligofructose supplementation of appetite and energy intake we asked the participants to complete a few VAS questionnaires on appetite and potential side effects and 3-day diet diaries at home. Participants recorded their food intake the last 3 days of each week at 0 g and at each level of oligofructose intake (Fig. 1A). A nutritionist instructed the participants how to complete the diet diaries at screening. Detailed instructions and pictures showing
Appetite study sessions within the metabolic unit
These studies were all conducted in the metabolic unit at the University of Surrey. Appetite study sessions were performed at the end of 0, 15, 35, and 55 g/day oligofructose periods. To limit the total blood loss during the study for ethical reasons, no acute appetite study sessions were performed at 25 g and 45 g. Twenty-four hours prior to the study day participants were asked to refrain from strenuous physical activity and consume no alcohol or caffeine containing drinks. Participants were
Blood samples
Venous blood for gut hormone measurements was collected in potassium EDTA tubes containing 200 kallikrein inhibiting units (KIU) aprotinin (Trasylol, Bayer, Newbury, UK) per mL blood, for glucose analysis into sodium fluoride/oxalate tubes, and for insulin analysis into potassium EDTA tubes. All blood samples were centrifuged for 10 min at 2000 g at 4 °C. Plasma was separated and stored at −20 °C until analysis.
Plasma glucose and insulin
Plasma glucose and insulin were measured in the Department of Clinical Biochemistry, Hammersmith Hospital, using an Abbott Architect ci8200 analyzer (Abbott Diagnostics, Maidenhead, UK) and a Axsym analyzer (Abbott Diagnostics, Maidenhead, UK) respectively. The glucose assay detection limit was 0.3 mmol/L with an intra-assay CV of 1%. The insulin assay detection limit was 7 pmol/L with an intra-assay CV of 2.6%.
Gut hormone radioimmunoassays
Samples were stored at −20 °C and thawed immediately before the assay. All samples were
Results
Twelve healthy participants (four men and eight women) were recruited for the study. Female participants were all pre-menopausal and not pregnant or lactating. Two women dropped out due to gastrointestinal side effects most likely related to the dietary fibre supplementation; one at the beginning of the 25 g period and another on day six of the 45 g period. The subjective appetite and energy intake results presented here are based on 11 participants (0–45 g oligofructose/day) and 10 participants
Glucose and insulin
There was no difference in fasting glucose (4.8 ± 0.1, 4.7 ± 0.1, 4.7 ± 0.1 and 4.8 ± 0.1 mmol/L for 0, 15, 35, and 55 g oligofructose, respectively, P = 0.315) or insulin (27.1 ± 3.1, 32.2 ± 3.1, 33.7 ± 3.1 and 31.7 ± 3.2 pmol/L for 0, 15, 35, and 55 g oligofructose, respectively, P = 0.329) concentrations between treatments. Postprandial plasma glucose and insulin AUCs480min were not significantly affected by treatment (Table 3).
Gut hormones
Due to the occurrence of gastrointestinal side effects at the higher doses in some
Discussion
Prevention of weight gain in adult humans is a major public health target. In this study we demonstrate the complex relationship between oligofructose supplementation and appetite regulation in normal weight humans. In summary, we found a significant decrease in hunger scores in free-living conditions; however, this was not associated with a significant change in energy intake. The effect of oligofructose supplementation on gut hormones was complex; there was a significant increase in plasma
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2020, Journal of Functional FoodsCitation Excerpt :Several studies have established the beneficial impact of oligofructose supplementation on commensal Bifidobacterium populations and enhancement of gut microbiome diversity (Meyer & Stasse-Wolthuis, 2009). More recent studies report potential benefits of oligofructose intake in overweight and obese individuals ranging from regulating appetite through managing gut hormone release (Cani et al., 2006; Parnell & Reimer, 2009; Pedersen et al., 2013), reduction in metabolic endotoxemia (Parnell, Klancic, & Reimer, 2017), however the link between oligofructose intake and weight loss is not yet fully established (Daud et al., 2014). The intervention also delivers chromium, in the form of chromium picolinate.
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2020, Journal of Functional FoodsCitation Excerpt :However, the exact impact of SCFAs on anorexic hormones excretion and energy intake are still not clear. A short-term human study with oligofructose supplementation at high dosage promoted SCFAs production in the colon and increased peptide YY (PYY) excretion but exerted no impact on energy intake (Pedersen et al., 2013). In the current study, reduced body weight gain and fat accumulation, and increased fecal SCFAs content were observed in HFD+MLE mice when compared to HFD mice, with no difference in energy intake between the two groups.
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Acknowledgements: We thank the participants in the study for their time. We thank Orafti, Tienen, Belgium, and DKSH Great Britain for providing the Beneo P95 and Heather E. Ford, Norlida Mat Daud and Paul R. Beck for their assistance with the PYY radioimmunoassay. We thank Shelagh Hampton and John Wright for their help in the metabolic unit at the University of Surrey, and Mandy Donaldson and John Meek for insulin and glucose assays. The authors’ responsibilities were as follows: CP designed the experiment, collected and analyzed the data, and wrote the manuscript. SL assisted in collection of data; VP assisted with radioimmunoassays and provided advice; MP: supervised and assisted with radioimmunoassays; LMM and GSF (principal investigator) contributed to the design of the experiment, supervised the Project, and revised the manuscript. MAG provided advice and reviewed the manuscript. All authors read and approved the final manuscript. None of the authors had a conflict of interest. Orafti and DKSH Great Britain gave the test product as a gift and had no influence on the study design, implementation, analyses, interpretation of the data, or the manuscript. CP and VP were funded by the European Commission’s Sixth Framework Program (FP6) under the NuSISCO programme. GSF is supported by an NIHR senior investigator award. The Section is funded by grants from the MRC, BBSRC, and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme.