title: Fructose overfeeding in first-degree relatives of type 2 diabetic patients impacts energy metabolism and mitochondrial functions in skeletal muscle.
abstract: The aim of the study was to assess the effects of a high-fructose diet (HFrD) on skeletal muscle transcriptomic response in healthy offspring of patients with type 2 diabetes, a subgroup of individuals prone to metabolic disorders.
  
  
  
  Ten healthy normal weight first-degree relatives of type 2 diabetic patients were submitted to a HFrD (+3.5 g fructose/kg fat-free mass per day) during 7 days. A global transcriptomic analysis was performed on skeletal muscle biopsies combined with in vitro experiments using primary myotubes. Transcriptomic analysis highlighted profound effects on fatty acid oxidation and mitochondrial pathways supporting the whole-body metabolic shift with the preferential use of carbohydrates instead of lipids. Bioinformatics tools pointed out possible transcription factors orchestrating this genomic regulation, such as PPARα and NR4A2. In vitro experiments in human myotubes suggested an indirect action of fructose in skeletal muscle, which seemed to be independent from lactate, uric acid, or nitric oxide.
  
  
  
  This study shows therefore that a large cluster of genes related to energy metabolism, mitochondrial function, and lipid oxidation was downregulated after 7 days of HFrD, thus supporting the concept that overconsumption of fructose-containing foods could contribute to metabolic deterioration in humans.
authors.affiliation: Lyon University, Oullins, France.|CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France.|CRNH Rhône-Alpes, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Seyssel
authors.affiliation: Lyon University, Oullins, France.|CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Meugnier
authors.affiliation: Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Kim-Anne
authors.initials: KA
authors.lastname: Lê
authors.affiliation: Lyon University, Oullins, France.|CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Durand
authors.affiliation: Lyon University, Oullins, France.|CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France.|CRNH Rhône-Alpes, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Disse
authors.affiliation: Lyon University, Oullins, France.|CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France.|CRNH Rhône-Alpes, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Blond
authors.affiliation: Lyon University, Oullins, France.|CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France.|Banque de Cellules et de Tissus, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pays
authors.affiliation: Lyon University, Oullins, France.|CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France.|Banque de Cellules et de Tissus, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Nataf
authors.affiliation: Genfit, Loos, France.
authors.forename: John
authors.initials: J
authors.lastname: Brozek
authors.affiliation: Lyon University, Oullins, France.|CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France.|CRNH Rhône-Alpes, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.affiliation: Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Luc
authors.initials: L
authors.lastname: Tappy
authors.affiliation: Lyon University, Oullins, France.|CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France.|CRNH Rhône-Alpes, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Laville
mesh_terms: D000328:Adult; D002460:Cell Line; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004032:Diet; D004734:Energy Metabolism; D005632:Fructose / Q000008:administration & dosage* / Q000009:adverse effects*; D020869:Gene Expression Profiling; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D055815:Young Adult
chemical_list: C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D047493:PPAR alpha; D005632:Fructose
keywords: Energy metabolism; Gene regulation; High-fructose diet; Lipid oxidation; Skeletal muscle