title: TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal muscle.
abstract: TWIST proteins are important for development of embryonic skeletal muscle and play a role in the metabolism of tumor and white adipose tissue. The impact of TWIST on metabolism in skeletal muscle is incompletely studied. Our aim was to assess the impact of TWIST1 and TWIST2 overexpression on glucose and lipid metabolism. In intact mouse muscle, overexpression of Twist reduced total glycogen content without altering glucose uptake. Expression of TWIST1 or TWIST2 reduced Pdk4 mRNA, while increasing mRNA levels of Il6, Tnfα, and Il1β. Phosphorylation of AKT was increased and protein abundance of acetyl CoA carboxylase (ACC) was decreased in skeletal muscle overexpressing TWIST1 or TWIST2. Glycogen synthesis and fatty acid oxidation remained stable in C2C12 cells overexpressing TWIST1 or TWIST2. Finally, skeletal muscle mRNA levels remain unaltered in ob/ob mice, type 2 diabetic patients, or in healthy subjects before and after 3 months of exercise training. Collectively, our results indicate that TWIST1 and TWIST2 are expressed in skeletal muscle. Overexpression of these proteins impacts proteins in metabolic pathways and mRNA level of cytokines. However, skeletal muscle levels of TWIST transcripts are unaltered in metabolic diseases.
authors: Section for Integrative PhysiologyDepartment of Molecular Medicine and SurgerySection for Integrative PhysiologyDepartment of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors: Jonathan M
authors: JM
authors: Mudry
authors: Section for Integrative PhysiologyDepartment of Molecular Medicine and SurgerySection for Integrative PhysiologyDepartment of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors: Julie
authors: J
authors: Massart
authors: Section for Integrative PhysiologyDepartment of Molecular Medicine and SurgerySection for Integrative PhysiologyDepartment of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors: Ferenc L M
authors: FL
authors: Szekeres
authors: Section for Integrative PhysiologyDepartment of Molecular Medicine and SurgerySection for Integrative PhysiologyDepartment of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden Section for Integrative PhysiologyDepartment of Molecular Medicine and SurgerySection for Integrative PhysiologyDepartment of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden Anna.Krook@ki.se.
authors: Anna
authors: A
authors: Krook
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D051879:Twist-Related Protein 1 / Q000502:physiology*
chemical_list: D009687:Nuclear Proteins; D012097:Repressor Proteins; C103173:TWIST1 protein, human; C486274:TWIST2 protein, human; D051879:Twist-Related Protein 1; D006003:Glycogen
keywords: TWIST; glycogen; metabolism; skeletal muscle