title: Synchronized human skeletal myotubes of lean, obese and type 2 diabetic patients maintain circadian oscillation of clock genes.
abstract: Cell and animal studies have demonstrated that circadian rhythm is governed by autonomous rhythmicity of clock genes. Although disturbances in circadian rhythm have been implicated in metabolic disease development, it remains unknown whether muscle circadian rhythm is altered in human models of type 2 diabetes. Here we used human primary myotubes (HPM) to investigate if rhythmicity of clock- and metabolic gene expression is altered in donors with obesity or type 2 diabetes compared to metabolically healthy donors. HPM were obtained from skeletal muscle biopsies of four groups: type 2 diabetic patients and their BMI- and age-matched obese controls and from lean, healthy and young endurance trained athletes and their age-matched sedentary controls. HPM were differentiated for 7 days before synchronization by serum shock followed by gene expression profiling over the next 72 hours. HPM display robust circadian rhythms in clock genes, but REVERBA displayed dampened rhythmicity in type 2 diabetes. Furthermore, rhythmicity in NAMPT and SIRT1 expression was only observed in HPM from trained athletes. Rhythmicity in expression of key-regulators of carbohydrate and lipid metabolism was modest. We demonstrate that in human skeletal muscle REVERBA/B, NAMPT and SIRT1 circadian rhythms are affected in donors of sedentary life style and poor health status.
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Hansen
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Silvie
authors.initials: S
authors.lastname: Timmers
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Moonen-Kornips
authors.affiliation: Institut Pasteur de Lille, Lille, France.|Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1011, Lille, France.|Univ. Lille, European Genomic Institute for Diabetes, Lille, France.
authors.forename: Helene
authors.initials: H
authors.lastname: Duez
authors.affiliation: Institut Pasteur de Lille, Lille, France.|Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1011, Lille, France.|Univ. Lille, European Genomic Institute for Diabetes, Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Matthijs K C
authors.initials: MK
authors.lastname: Hesselink
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
mesh_terms: D001706:Biopsy; D056926:CLOCK Proteins / Q000235:genetics*; D002478:Cells, Cultured; D002940:Circadian Rhythm; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D015444:Exercise; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D056926:CLOCK Proteins