title: Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor γ and Glucagon-Like Peptide-1.
abstract: The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs), have been suggested to play an important role. Recently, we showed that SCFAs protect against the metabolic syndrome via a signaling cascade that involves peroxisome proliferator-activated receptor (PPAR) γ repression and AMP-activated protein kinase (AMPK) activation. In this study we investigated the molecular mechanism via which the dietary fiber guar gum protects against the metabolic syndrome. C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber guar gum for 12 weeks and effects on lipid and glucose metabolism were studied. We demonstrate that, like SCFAs, also guar gum protects against high-fat diet-induced metabolic abnormalities by PPARγ repression, subsequently increasing mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the activation of AMPK and culminating in enhanced oxidative metabolism in both liver and adipose tissue. Moreover, guar gum markedly increased peripheral glucose clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like peptide-1. Overall, this study provides novel molecular insights into the beneficial effects of guar gum on the metabolic syndrome and strengthens the potential role of guar gum as a dietary-fiber intervention.
authors: 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: Gijs
authors: G
authors: den Besten
authors: 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: Albert
authors: A
authors: Gerding
authors: Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Theo H
authors: TH
authors: van Dijk
authors: 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: Jolita
authors: J
authors: Ciapaite
authors: 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, P.O. Box 557, 6700 AN Wageningen, The Netherlands.
authors: Aycha
authors: A
authors: Bleeker
authors: 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, P.O. Box 557, 6700 AN Wageningen, The Netherlands.
authors: Karen
authors: K
authors: van Eunen
authors: 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: Rick
authors: R
authors: Havinga
authors: 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; Top Institute Food and Nutrition, P.O. Box 557, 6700 AN Wageningen, The Netherlands.
authors: Albert K
authors: AK
authors: Groen
authors: 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; Top Institute Food and Nutrition, P.O. Box 557, 6700 AN Wageningen, The Netherlands.
authors: Dirk-Jan
authors: DJ
authors: Reijngoud
authors: 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, P.O. Box 557, 6700 AN Wageningen, The Netherlands.
authors: Barbara M
authors: BM
authors: Bakker
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002153:Calorimetry, Indirect; D002432:Cecum / Q000737:chemistry; D004043:Dietary Fiber / Q000627:therapeutic use*; D005232:Fatty Acids, Volatile / Q000032:analysis / Q000378:metabolism*; D005685:Galactans / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000502:physiology*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D008297:Male; D008351:Mannans / Q000627:therapeutic use*; D024821:Metabolic Syndrome / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism / Q000502:physiology*; D053149:Plant Gums / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D004043:Dietary Fiber; D005232:Fatty Acids, Volatile; D005685:Galactans; D008351:Mannans; D047495:PPAR gamma; D053149:Plant Gums; D052216:Glucagon-Like Peptide 1; C007894:guar gum; D055372:AMP-Activated Protein Kinases