title: Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men.
abstract: Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men. In this randomized, double-blind crossover trial, six overweight/obese men [body mass index (BMI) 25-35 kg/m2] underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions. A feeding catheter was endoscopically positioned at the beginning of each period and remained in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were repeatedly collected for 2 h during fasting and postprandial conditions. Distal colonic 180 mmol/l acetate infusions increased fasting fat oxidation (1.78±0.28 compared with -0.78±0.89 g fat 2 h-1, P=0.015), fasting peptide YY (PYY, P=0.01) and postprandial glucose and insulin concentrations (P<0.05), and tended to increase fasting plasma acetate (P=0.069) compared with placebo. Distal 100 mmol/l acetate administration tended to decrease fasting tumour necrosis factor-α (TNF-α; P=0.067) compared with placebo. In contrast, proximal colonic acetate infusions showed no effects on substrate metabolism, circulating hormones or inflammatory markers. In conclusion distal colonic acetate infusions affected whole-body substrate metabolism, with a pronounced increase in fasting fat oxidation and plasma PYY. Modulating colonic acetate may be a nutritional target to treat or prevent metabolic disorders.
authors.affiliation: Top Institute Food and Nutrition, Wageningen, 6700 AN, The Netherlands Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, 6299 ER, The Netherlands.
authors.forename: Christina M
authors.initials: CM
authors.lastname: van der Beek
authors.affiliation: Top Institute Food and Nutrition, Wageningen, 6700 AN, The Netherlands Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, 6229 ER, The Netherlands Emanuel.canfora@maastrichtuniversity.nl.
authors.forename: Emanuel E
authors.initials: EE
authors.lastname: Canfora
authors.affiliation: Top Institute Food and Nutrition, Wageningen, 6700 AN, The Netherlands Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, 6299 ER, The Netherlands.
authors.forename: Kaatje
authors.initials: K
authors.lastname: Lenaerts
authors.affiliation: Top Institute Food and Nutrition, Wageningen, 6700 AN, The Netherlands Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, 6229 ER, The Netherlands.
authors.forename: Freddy J
authors.initials: FJ
authors.lastname: Troost
authors.affiliation: Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, 6299 ER, The Netherlands Department of HPB Surgery and Liver Transplantation, Institute of Liver and Digestive Health, University College London, London WC1 6HX, U.K.
authors.forename: Steven W M Olde
authors.initials: SWMO
authors.lastname: Damink
authors.affiliation: NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen 2200, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Top Institute Food and Nutrition, Wageningen, 6700 AN, The Netherlands Department of Internal Medicine, Division of Gastroenterology-Hepatology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, 6229 ER, The Netherlands.
authors.forename: Ad A M
authors.initials: AAM
authors.lastname: Masclee
authors.affiliation: Top Institute Food and Nutrition, Wageningen, 6700 AN, The Netherlands Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, 6299 ER, The Netherlands.
authors.forename: Cornelis H C
authors.initials: CHC
authors.lastname: Dejong
authors.affiliation: Top Institute Food and Nutrition, Wageningen, 6700 AN, The Netherlands Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, 6229 ER, The Netherlands.
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D000328:Adult; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004734:Energy Metabolism; D005223:Fats / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D050177:Overweight / Q000188:drug therapy* / Q000378:metabolism; D010084:Oxidation-Reduction; D019894:Peptide YY / Q000378:metabolism; D055815:Young Adult
chemical_list: D000085:Acetates; D005223:Fats; D007328:Insulin; D019894:Peptide YY
keywords: fatty acid oxidation; intestinal hormones; metabolic control; obesity; short-chain fatty acids