title: The short-chain fatty acid uptake fluxes by mice on a guar gum supplemented diet associate with amelioration of major biomarkers of the metabolic syndrome.
abstract: Studies with dietary supplementation of various types of fibers have shown beneficial effects on symptoms of the metabolic syndrome. Short-chain fatty acids (SCFAs), the main products of intestinal bacterial fermentation of dietary fiber, have been suggested to play a key role. Whether the concentration of SCFAs or their metabolism drives these beneficial effects is not yet clear. In this study we investigated the SCFA concentrations and in vivo host uptake fluxes in the absence or presence of the dietary fiber guar gum. C57Bl/6J mice were fed a high-fat diet supplemented with 0%, 5%, 7.5% or 10% of the fiber guar gum. To determine the effect on SCFA metabolism, 13C-labeled acetate, propionate or butyrate were infused into the cecum of mice for 6 h and the isotopic enrichment of cecal SCFAs was measured. The in vivo production, uptake and bacterial interconversion of acetate, propionate and butyrate were calculated by combining the data from the three infusion experiments in a single steady-state isotope model. Guar gum treatment decreased markers of the metabolic syndrome (body weight, adipose weight, triglycerides, glucose and insulin levels and HOMA-IR) in a dose-dependent manner. In addition, hepatic mRNA expression of genes involved in gluconeogenesis and fatty acid synthesis decreased dose-dependently by guar gum treatment. Cecal SCFA concentrations were increased compared to the control group, but no differences were observed between the different guar gum doses. Thus, no significant correlation was found between cecal SCFA concentrations and metabolic markers. In contrast, in vivo SCFA uptake fluxes by the host correlated linearly with metabolic markers. We argue that in vivo SCFA fluxes, and not concentrations, govern the protection from the metabolic syndrome by dietary fibers.
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics & Systems Biology Center for Energy Metabolism and Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Netherlands Consortium for Systems Biology, Amsterdam, The Netherlands.
authors.forename: Gijs
authors.initials: G
authors.lastname: den Besten
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics & Systems Biology Center for Energy Metabolism and Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Havinga
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics & Systems Biology Center for Energy Metabolism and Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Aycha
authors.initials: A
authors.lastname: Bleeker
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics & Systems Biology Center for Energy Metabolism and Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Shodhan
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Gerding
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics & Systems Biology Center for Energy Metabolism and Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Netherlands Consortium for Systems Biology, Amsterdam, The Netherlands; Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Karen
authors.initials: K
authors.lastname: van Eunen
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics & Systems Biology Center for Energy Metabolism and Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Netherlands Consortium for Systems Biology, Amsterdam, The Netherlands.
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics & Systems Biology Center for Energy Metabolism and Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Netherlands Consortium for Systems Biology, Amsterdam, The Netherlands.
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: Reijngoud
authors.affiliation: Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics & Systems Biology Center for Energy Metabolism and Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Netherlands Consortium for Systems Biology, Amsterdam, The Netherlands.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bakker
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002432:Cecum / Q000378:metabolism; D059305:Diet, High-Fat / Q000379:methods; D004043:Dietary Fiber / Q000378:metabolism*; D019587:Dietary Supplements; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005685:Galactans / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008351:Mannans / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D053149:Plant Gums / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004043:Dietary Fiber; D005232:Fatty Acids, Volatile; D005685:Galactans; D007328:Insulin; D008351:Mannans; D053149:Plant Gums; D014280:Triglycerides; C007894:guar gum