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Randomized Controlled Trial
. 2017 May 24;7(1):2360.
doi: 10.1038/s41598-017-02546-x.

Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial

Emanuel E Canfora  1   2 , Christina M van der Beek  3   4 , Johan W E Jocken  5   3 , Gijs H Goossens  5   3 , Jens J Holst  6 , Steven W M Olde Damink  4   7 , Kaatje Lenaerts  3   4 , Cornelis H C Dejong  3   4   8 , Ellen E Blaak  5   3
Affiliations
Randomized Controlled Trial

Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial (V体育平台登录)

Emanuel E Canfora et al. Sci Rep. .

Abstract

Short-chain fatty acids (SCFA), formed by microbial fermentation, are believed to be involved in the aetiology of obesity and diabetes. This study investigated the effects of colonic administration of physiologically relevant SCFA mixtures on human substrate and energy metabolism. In this randomized, double-blind, crossover study, twelve normoglycaemic men (BMI 25-35 kg/m2) underwent four investigational days, during which SCFA mixtures (200 mmol/L) high in either acetate (HA), propionate (HP), butyrate (HB) or placebo (PLA) were rectally administered during fasting and postprandial conditions (oral glucose load). Before and for two hours after colonic infusions, indirect calorimetry was performed and blood samples were collected. All three SCFA mixtures increased fasting fat oxidation (P < 0. 01), whilst resting energy expenditure increased after HA and HP compared with PLA (P < 0. 05). In addition, all three SCFA mixtures increased fasting and postprandial plasma peptide YY (PYY) concentrations, and attenuated fasting free glycerol concentrations versus PLA (P < 0. 05) VSports手机版. Colonic infusions of SCFA mixtures, in concentrations and ratios reached after fibre intake, increased fat oxidation, energy expenditure and PYY, and decreased lipolysis in overweight/obese men. Human intervention studies are warranted to investigate whether these effects translate into long-term benefits for body weight control and insulin sensitivity in the obese insulin resistant state. .

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Effect of colonic administration of SCFA mixtures on fasting and postprandial energy expenditure (A,B), fat oxidation (C,D), and carbohydrate oxidation (E,F) (A) Resting (t0–t120 min) and postprandial (t180–t300 min) energy expenditure after colonic SCFA infusions. (B) iAUC for resting (t0–t120 min) energy expenditure following colonic SCFA infusions. Overall treatment effect for resting energy expenditure P = 0.049 (period P = 0.933, carry-over P = 0.571). (C) Fasting (t0–t120 min) and postprandial (t180–t300 min) fat oxidation after colonic SCFA infusions. (D) iAUC for fasting (t0–t120 min) fat oxidation following colonic SCFA infusions. Overall treatment effect for fasting fat oxidation P < 0.001 (period P = 0.325, carry-over P = 0.235). (E) Fasting (t0–t120 min) and postprandial (t180–t300 min) carbohydrate oxidation after colonic SCFA infusions. (F) iAUC for fasting (t0–t120 min) carbohydrate oxidation following colonic SCFA infusions. Overall treatment effect for fasting carbohydrate oxidation P = 0.010 (period P = 0.315, carry-over P = 0.154). Values are means ± SEMs (n = 12). Statistical significance indicated as asterisk (*) when ***P < 0.001, **P < 0.01, *P < 0.05.
Figure 2
Figure 2
Effect of colonic administration of SCFA mixtures on fasting and postprandial plasma acetate (A,B), propionate (C,D), and butyrate (E–G) concentrations (A) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma acetate concentrations after colonic SCFA infusions. (B) iAUC for fasting (t0–t120 min) plasma acetate following colonic SCFA infusions. Overall treatment effect for fasting plasma acetate P = 0.051 (period P = 0.338, carry-over P = 0.898). (C) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma propionate concentrations after colonic SCFA infusions. (D) iAUC for postprandial (t180–t300 min) plasma propionate following colonic SCFA infusions. Overall treatment effect for postprandial plasma propionate P = 0.068 (period P = 0.781, carry-over P = 0.896). (E) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma butyrate concentrations after colonic SCFA infusions. (F) iAUC for fasting (t0–t120 min) plasma butyrate following colonic SCFA infusions. Overall treatment effect for fasting plasma butyrate P < 0.001 (period P = 0.997, carry-over P = 0.879) (G) iAUC for postprandial (t180–t300 min) plasma butyrate following colonic SCFA infusions. Overall treatment effect for postprandial plasma butyrate P = 0.032 (period P = 0.754, carry-over P = 0.971). Values are means ± SEMs (n = 12). Statistical significance indicated as asterisk (*) when ***P < 0.001, **P < 0.01, *P < 0.05 and as hashtag when # P < 0.10.
Figure 3
Figure 3
Effect of colonic administration of SCFA mixtures on fasting and postprandial plasma glucose (A), insulin (B) and free glycerol (C,D) concentrations (A) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma glucose concentrations after colonic SCFA infusions. (B) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma insulin concentrations after colonic SCFA infusions. (C) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma free glycerol concentrations after colonic SCFA infusions. (D) iAUC for fasting (t0–t120 min) plasma free glycerol following colonic SCFA infusion. Overall treatment effect for free glycerol P = 0.030 (period P = 0.483, carry-over P = 0.832). Values are means ± SEMs (n = 12). Statistical significance indicated as asterisk (*) when **P < 0.01, *P < 0.05.
Figure 4
Figure 4
Effect of colonic administration of SCFA mixtures on fasting and postprandial plasma PYY (A–C), GLP-1 (D) and ANGPTL4 (F) (A) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma PYY concentrations after colonic SCFA infusions. (B) iAUC for fasting (t0–t120 min) plasma PYY following colonic SCFA infusion. Overall treatment effect fasting PYY P = 0.011 (period P = 0.557, carry-over P = 0.553). (C) iAUC for postprandial (t120–t300 min) plasma PYY following colonic SCFA infusion. Overall treatment effect postprandial PYY P < 0.001 (period P = 0.595, carry-over P = 0.184). (D) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma GLP-1 concentrations after colonic SCFA infusions. (E) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma ANGTPL4 concentrations after colonic SCFA infusions. Values are means ± SEMs (n = 12). Statistical significance indicated as asterisk (*) when ***P < 0.001 and **P < 0.01 and *P < 0.05.
Figure 5
Figure 5
Effect of colonic administration of SCFA mixtures on fasting and postprandial plasma inflammatory cytokines (A) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma IL-1β concentrations after colonic SCFA infusions. (B) iAUC for fasting (t0–t120 min) plasma IL-1β following colonic SCFA infusion. Values are means ± SEMs (n = 10, for two volunteers IL-1β concentrations were not detectable). Overall treatment effect for fasting IL-1β P = 0.068 (period P = 0.626, carry-over P = 0.841). (C) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma TNF-α after colonic SCFA infusions. Values are means ± SEMs (n = 12).) (D) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma IL-6 after colonic SCFA infusions. Values are means ± SEMs (n = 11, for one participant IL-6 concentrations were not detectable). (E) Fasting (t0–t120 min) and postprandial (t180–t300 min) plasma IL-8 after colonic SCFA infusions. Values are means ± SEMs (n = 12). Statistical significance indicated as asterisk (*) when *P < 0.05 and as hashtag when # P < 0.10.
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