Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide. 2017

Robin Mesnage, and George Renney, and Gilles-Eric Séralini, and Malcolm Ward, and Michael N Antoniou
Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences &Medicine, Department of Medical and Molecular Genetics, 8th Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, United Kingdom.

The impairment of liver function by low environmentally relevant doses of glyphosate-based herbicides (GBH) is still a debatable and unresolved matter. Previously we have shown that rats administered for 2 years with 0.1 ppb (50 ng/L glyphosate equivalent dilution; 4 ng/kg body weight/day daily intake) of a Roundup GBH formulation showed signs of enhanced liver injury as indicated by anatomorphological, blood/urine biochemical changes and transcriptome profiling. Here we present a multiomic study combining metabolome and proteome liver analyses to obtain further insight into the Roundup-induced pathology. Proteins significantly disturbed (214 out of 1906 detected, q < 0.05) were involved in organonitrogen metabolism and fatty acid β-oxidation. Proteome disturbances reflected peroxisomal proliferation, steatosis and necrosis. The metabolome analysis (55 metabolites altered out of 673 detected, p < 0.05) confirmed lipotoxic conditions and oxidative stress by showing an activation of glutathione and ascorbate free radical scavenger systems. Additionally, we found metabolite alterations associated with hallmarks of hepatotoxicity such as γ-glutamyl dipeptides, acylcarnitines, and proline derivatives. Overall, metabolome and proteome disturbances showed a substantial overlap with biomarkers of non-alcoholic fatty liver disease and its progression to steatohepatosis and thus confirm liver functional dysfunction resulting from chronic ultra-low dose GBH exposure.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005998 Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Aminoacetic Acid,Glycine, Monopotassium Salt,Glycine Carbonate (1:1), Monosodium Salt,Glycine Carbonate (2:1), Monolithium Salt,Glycine Carbonate (2:1), Monopotassium Salt,Glycine Carbonate (2:1), Monosodium Salt,Glycine Hydrochloride,Glycine Hydrochloride (2:1),Glycine Phosphate,Glycine Phosphate (1:1),Glycine Sulfate (3:1),Glycine, Calcium Salt,Glycine, Calcium Salt (2:1),Glycine, Cobalt Salt,Glycine, Copper Salt,Glycine, Monoammonium Salt,Glycine, Monosodium Salt,Glycine, Sodium Hydrogen Carbonate,Acid, Aminoacetic,Calcium Salt Glycine,Cobalt Salt Glycine,Copper Salt Glycine,Hydrochloride, Glycine,Monoammonium Salt Glycine,Monopotassium Salt Glycine,Monosodium Salt Glycine,Phosphate, Glycine,Salt Glycine, Monoammonium,Salt Glycine, Monopotassium,Salt Glycine, Monosodium
D006540 Herbicides Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE. Algaecide,Algicide,Herbicide,Algaecides,Algicides
D000097797 Glyphosate Active compound in herbicidal formulations that inhibits 3-PHOSPHOSHIKIMATE 1-CARBOXYVINYLTRANSFERASE. Gliphosate,Glyphosate Hydrochloride (2:1),Glyphosate, Calcium Salt,Glyphosate, Calcium Salt (1:1),Glyphosate, Copper (2+) Salt,Glyphosate, Dilithium Salt,Glyphosate, Disodium Salt,Glyphosate, Magnesium Salt,Glyphosate, Magnesium Salt (2:1),Glyphosate, Monoammonium Salt,Glyphosate, Monopotassium Salt,Glyphosate, Monosodium Salt,Glyphosate, Sodium Salt,Glyphosate, Zinc Salt,Yerbimat,Kalach 360 SL,N-(phosphonomethyl)glycine,Roundup
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D055432 Metabolomics The systematic identification and quantitation of all the metabolic products of a cell, tissue, organ, or organism under varying conditions. The METABOLOME of a cell or organism is a dynamic collection of metabolites which represent its net response to current conditions. Metabonomics,Metabolomic,Metabonomic
D040901 Proteomics The systematic study of the complete complement of proteins (PROTEOME) of organisms. Peptidomics
D065626 Non-alcoholic Fatty Liver Disease Fatty liver finding without excessive ALCOHOL CONSUMPTION. Fatty Liver, Nonalcoholic,NAFLD,Nonalcoholic Fatty Liver Disease,Nonalcoholic Steatohepatitis,Fatty Livers, Nonalcoholic,Liver, Nonalcoholic Fatty,Livers, Nonalcoholic Fatty,Non alcoholic Fatty Liver Disease,Nonalcoholic Fatty Liver,Nonalcoholic Fatty Livers,Nonalcoholic Steatohepatitides,Steatohepatitides, Nonalcoholic,Steatohepatitis, Nonalcoholic

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