title: Methionine restriction affects the phenotypic and transcriptional response of rainbow trout (Oncorhynchus mykiss) to carbohydrate-enriched diets.
abstract: Mammalian studies report that methionine restriction (MR) as a dietary regimen extends life span, delays the onset of age-related diseases and enhances fat oxidation in obese subjects with metabolic syndromes. However, the underlying cellular signalling pathways are poorly understood. Rainbow trout (Oncorhynchus mykiss) is a glucose-intolerant species, providing an excellent model for the study of carbohydrate metabolism. MR diets in combination with 12 % (+/-) and 22 % (+/-) carbohydrate-rich meals were fed to rainbow trout for a period of 8 weeks and phenotypic and transcript expression changes in the liver and white muscle were assessed. Fish fed MR diets, irrespective of carbohydrate load, were shown to abolish the glucose-intolerant phenotype 6 h post-feeding. There was a distinct switch in glucose and glycogen content in the liver of fish fed MR diets, with a significantly higher concentration of glycogen, suggesting reduced glycolytic capacity. Transcriptional responses to MR demonstrated decreased expression of hepatic fatty acid synthase, sterol regulatory binding protein 1, PPARγ coactivator 1-α and PPARα, indicative of a reduction in the de novo synthesis of fatty acids and cholesterol, and a potential decrease in hepatic fat oxidative capacity. Muscle adenylate charge was depressed under MR, and increased expression of AMP-activated protein kinase α1 was detected, indicative of reduced energy availability. Total DNA methylation showed that carbohydrate load, rather than MR, dictated hypomethylation of genomic DNA. This is the first study which demonstrates that MR can abolish a glucose-intolerant phenotype in trout, and identifies trout as a suitable model for studying metabolic syndromes.
authors.affiliation: Department of Biology, Centre for Advanced Research in Environmental Genomics, University of Ottawa, 30 Marie Curie, Ottawa, Canada, ON K1N 6N5.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Craig
authors.affiliation: Department of Biology, Centre for Advanced Research in Environmental Genomics, University of Ottawa, 30 Marie Curie, Ottawa, Canada, ON K1N 6N5.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Moon
mesh_terms: D000818:Animals; D017756:Aquaculture; D019175:DNA Methylation; D004040:Dietary Carbohydrates / Q000009:adverse effects; D015536:Down-Regulation; D004734:Energy Metabolism; D044127:Epigenesis, Genetic; D005260:Female; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D060434:Herbivory; D050155:Lipogenesis; D008099:Liver / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008715:Methionine / Q000009:adverse effects / Q000378:metabolism*; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology / Q000378:metabolism*; D017686:Oncorhynchus mykiss / Q000254:growth & development / Q000378:metabolism*; D010101:Oxygen Consumption; D014158:Transcription, Genetic
chemical_list: D004040:Dietary Carbohydrates; D029941:Fish Proteins; D008112:Liver Glycogen; D008715:Methionine; D005947:Glucose