Adaptations to excess choline in insulin resistant and Pcyt2 deficient skeletal muscle.
Journal:
Biochemistry and cell biology = Biochimie et biologie cellulaire
PMID:
28068143
Abstract
It was hypothesized that choline supplementation in insulin resistant (IR) CTP:phosphoethanolamine cytidylyltransferase deficient (Pcyt2) mice would ameliorate muscle function by remodeling glucose and fatty acid (FA) metabolism. Pcyt2 mice either received no treatment or were allowed access to 2 mg/mL choline in drinking water for 4 weeks. Skeletal muscle was harvested from choline treated and untreated mice. Lipid analysis and metabolic gene expression and signaling pathways were compared between untreated Pcyt2 mice, treated Pcyt2 mice, and Pcyt2 mice. The major positive effect of choline supplementation on IR muscle was the reduction of glucose utilization for FA and triglyceride (TAG) synthesis and increased muscle glucose storage as glycogen. Choline reduced the expression of genes for FA and TAG formation (Scd1, Fas, Srebp1c, Dgat1/2), upregulated the genes for FA oxidation (Cpt1, Pparα, Pgc1α), and had minor effects on phospholipid and lipolysis genes. Pcyt2 muscle had reduced insulin signaling (IRS1), autophagy (LC3), and choline transport (CTL1) proteins that were restored by choline treatment. Additionally, choline activated AMPK and Akt while inhibiting mTORC1 phosphorylation. These data established that choline supplementation could restore muscle glucose metabolism by reducing lipogenesis and improving mitochondrial and intracellular signaling for protein and energy metabolism in insulin resistant Pcyt2 deficient mice.
Authors
Keywords
Adaptation, Physiological
Administration, Oral
Animals
Carnitine O-Palmitoyltransferase
Choline
Diacylglycerol O-Acyltransferase
fas Receptor
Fatty Acids
Gene Expression Regulation
Glucose
Insulin Receptor Substrate Proteins
Insulin Resistance
Lipogenesis
Mice
Mice, Knockout
Microtubule-Associated Proteins
Muscle, Skeletal
Organic Cation Transport Proteins
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
PPAR alpha
RNA Nucleotidyltransferases
Signal Transduction
Stearoyl-CoA Desaturase
Sterol Regulatory Element Binding Protein 1
Triglycerides