Kevin Seyssel1,2,3, Emmanuelle Meugnier1,2, Kim-Anne Lê4, Christine Durand1,2, Emmanuel Disse1,2,3, Emilie Blond1,2,3, Laurent Pays1,2,5, Serge Nataf1,2,5, John Brozek6, Hubert Vidal1,2,3, Luc Tappy4, Martine Laville1,2,3. 1. Lyon University, Oullins, France. 2. CarMeN Laboratory and CENS, Claude Bernard University, INSA Lyon, Oullins, France. 3. CRNH Rhône-Alpes, Centre Hospitalier Lyon-Sud, Pierre Bénite, France. 4. Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. 5. Banque de Cellules et de Tissus, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France. 6. Genfit, Loos, France.
Abstract
SCOPE: 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. METHODS AND RESULTS: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. CONCLUSION: 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.
RCT Entities:
SCOPE: 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. METHODS AND RESULTS: Ten healthy normal weight first-degree relatives of type 2 diabeticpatients 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. CONCLUSION: 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: Desiree M Sigala; Bettina Hieronimus; Valentina Medici; Vivien Lee; Marinelle V Nunez; Andrew A Bremer; Chad L Cox; Candice A Price; Yanet Benyam; Yasser Abdelhafez; John P McGahan; Nancy L Keim; Michael I Goran; Giovanni Pacini; Andrea Tura; Claude B Sirlin; Abhijit J Chaudhari; Peter J Havel; Kimber L Stanhope Journal: Nutrients Date: 2022-04-15 Impact factor: 6.706
Authors: M Balakumar; L Raji; D Prabhu; C Sathishkumar; P Prabu; V Mohan; M Balasubramanyam Journal: Mol Cell Biochem Date: 2016-10-03 Impact factor: 3.396