title: Metabolic adaptations to HFHS overfeeding: how whole body and tissues postprandial metabolic flexibility adapt in Yucatan mini-pigs.
abstract: OBJECTIVE
  In the present study, we aimed to metabolically characterize the postprandial adaptations of the major tissues involved in energy, lipids and amino acids metabolisms in mini-pigs.
  
  
  METHODS
  Mini-pigs were fed on high-fat-high-sucrose (HFHS) diet for 2 months and several tissues explored for metabolic analyses. Further, the urine metabolome was followed over the time to picture the metabolic adaptations occurring at the whole body level following overfeeding.
  
  
  RESULTS
  After 2 months of HFHS consumption, mini-pigs displayed an obese phenotype characterized by high circulating insulin, triglycerides and cholesterol levels. At the tissue level, a general (muscle, adipose tissue, intestine) reduction in the capacity to phosphorylate glucose was observed. This was also supported by the enhanced hepatic gluconeogenesis potential, despite the concomitant normoglycaemia, suggesting that the high circulating insulin levels would be enough to maintain glucose homoeostasis. The HFHS feeding also resulted in a reduced capacity of two other pathways: the de novo lipogenesis, and the branched-chain amino acids transamination. Finally, the follow-up of the urine metabolome over the time allowed determining breaking points in the metabolic trajectory of the animals.
  
  
  CONCLUSIONS
  Several features confirmed the pertinence of the animal model, including increased body weight, adiposity and porcine obesity index. At the metabolic level, we observed a perturbed glucose and amino acid metabolism, known to be related to the onset of the obesity. The urine metabolome analyses revealed several metabolic pathways potentially involved in the obesity onset, including TCA (citrate, pantothenic acid), amino acids catabolism (cysteine, threonine, leucine).
authors: Unité de Nutrition Humaine, Clermont Université, Université d'Auvergne, BP 10448, 63000, Clermont-Ferrand, France. sergio.polakof@clermont.inra.fr.|UMR 1019, UNH, CRNH Auvergne, INRA, 63000, Clermont-Ferrand, France. sergio.polakof@clermont.inra.fr.
authors: Sergio
authors: S
authors: Polakof
authors: Unité de Nutrition Humaine, Clermont Université, Université d'Auvergne, BP 10448, 63000, Clermont-Ferrand, France.|UMR 1019, UNH, CRNH Auvergne, INRA, 63000, Clermont-Ferrand, France.
authors: Didier
authors: D
authors: Rémond
authors: Unité de Microbiologie, UR454, INRA, 63122, Saint Genès Champanelle, France.
authors: Annick
authors: A
authors: Bernalier-Donadille
authors: Unité de Nutrition Humaine, Clermont Université, Université d'Auvergne, BP 10448, 63000, Clermont-Ferrand, France.|UMR 1019, UNH, CRNH Auvergne, INRA, 63000, Clermont-Ferrand, France.
authors: Mathieu
authors: M
authors: Rambeau
authors: Unité de Nutrition Humaine, Clermont Université, Université d'Auvergne, BP 10448, 63000, Clermont-Ferrand, France.|UMR 1019, UNH, CRNH Auvergne, INRA, 63000, Clermont-Ferrand, France.|UMR 1019, Plateforme d'Exploration du Métabolisme, UNH, INRA, 63000, Clermont-Ferrand, France.
authors: Estelle
authors: E
authors: Pujos-Guillot
authors: Unité de Nutrition Humaine, Clermont Université, Université d'Auvergne, BP 10448, 63000, Clermont-Ferrand, France.|UMR 1019, UNH, CRNH Auvergne, INRA, 63000, Clermont-Ferrand, France.
authors: Blandine
authors: B
authors: Comte
authors: Unité de Nutrition Humaine, Clermont Université, Université d'Auvergne, BP 10448, 63000, Clermont-Ferrand, France.|UMR 1019, UNH, CRNH Auvergne, INRA, 63000, Clermont-Ferrand, France.
authors: Dominique
authors: D
authors: Dardevet
authors: Unité de Nutrition Humaine, Clermont Université, Université d'Auvergne, BP 10448, 63000, Clermont-Ferrand, France.|UMR 1019, UNH, CRNH Auvergne, INRA, 63000, Clermont-Ferrand, France.
authors: Isabelle
authors: I
authors: Savary-Auzeloux
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000008:administration & dosage* / Q000009:adverse effects; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006963:Hyperphagia; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism; D055432:Metabolomics; D010766:Phosphorylation; D019518:Postprandial Period / Q000502:physiology; D013552:Swine; D013556:Swine, Miniature; D014280:Triglycerides / Q000097:blood; D014556:Urine / Q000737:chemistry
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D019422:Dietary Sucrose; D007328:Insulin; D014280:Triglycerides; D002784:Cholesterol; D005947:Glucose
keywords: Glucose and lipid metabolism; High-fat–high-sucrose diet; Metabolomics; Mini-pigs; Postprandial