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Pcyt2 deficiency causes age-dependant development of nonalcoholic steatohepatitis and insulin resistance that could be attenuated with phosphoethanolamine

Grapentine, Sophie ; Singh, Rathnesh K ; Basu, Poulami ; Sivanesan, Sugashan ; Mattos, Gabriela ; Oresajo, Oreoluwa ; Cheema, Jasmine ; Demeke, Wendwesen ; Dolinsky, Vernon W ; Bakovic, Marica

Scientific reports, 2022-01, Vol.12 (1), p.1048-1048 [Periódico revisado por pares]

England: Nature Publishing Group UK

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Pcyt2 deficiency causes age-dependant development of nonalcoholic steatohepatitis and insulin resistance that could be attenuated with phosphoethanolamine
Autor: Grapentine, Sophie ; Singh, Rathnesh K ; Basu, Poulami ; Sivanesan, Sugashan ; Mattos, Gabriela ; Oresajo, Oreoluwa ; Cheema, Jasmine ; Demeke, Wendwesen ; Dolinsky, Vernon W ; Bakovic, Marica
Assuntos: Aging ; Animals ; Ethanolamines - administration & dosage ; Fatty Acids - metabolism ; Glucose - metabolism ; Insulin Resistance ; Mice ; Mice, Knockout ; Non-alcoholic Fatty Liver Disease - drug therapy ; Non-alcoholic Fatty Liver Disease - enzymology ; Non-alcoholic Fatty Liver Disease - genetics ; Non-alcoholic Fatty Liver Disease - metabolism ; RNA Nucleotidyltransferases - deficiency ; RNA Nucleotidyltransferases - genetics
É parte de: Scientific reports, 2022-01, Vol.12 (1), p.1048-1048
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SourceType-Scholarly Journals-1
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Descrição: The mechanisms of NASH development in the context of age and genetics are not fully elucidated. This study investigates the age-dependent liver defects during NASH development in mice with heterozygous deletion of Pcyt2 (Pcyt2 ), the rate limiting enzyme in phosphatidylethanolamine (PE) synthesis. Further, the therapeutic potential of Pcyt2 substrate, phosphoethanolamine (PEtn), is examined. Pcyt2 were investigated at 2 and 6-8 months (mo) of age and in addition, 6-mo old Pcyt2 with developed NASH were supplemented with PEtn for 8 weeks and glucose and fatty acid metabolism, insulin signaling, and inflammation were examined. Heterozygous ablation of Pcyt2 causes changes in liver metabolic regulators from young age, prior to the development of liver disease which does not occur until adulthood. Only older Pcyt2 experiences perturbed glucose and fatty acid metabolism. Older Pcyt2 liver develops NASH characterized by increased glucose production, accumulation of TAG and glycogen, and increased inflammation. Supplementation with PEtn reverses Pcyt2 steatosis, inflammation, and other aspects of NASH, showing that was directly caused by Pcyt2 deficiency. Pcyt2 deficiency is a novel mechanism of metabolic dysregulation due to reduced membrane ethanolamine phospholipid synthesis, and the metabolite PEtn offers therapeutic potential for NASH reversion.
Editor: England: Nature Publishing Group UK
Idioma: Inglês

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Pcyt2 deficiency causes age-dependant development of nonalcoholic steatohepatitis and insulin resistance that could be attenuated with phosphoethanolamine

Grapentine, Sophie ; Singh, Rathnesh K ; Basu, Poulami ; Sivanesan, Sugashan ; Mattos, Gabriela ; Oresajo, Oreoluwa ; Cheema, Jasmine ; Demeke, Wendwesen ; Dolinsky, Vernon W ; Bakovic, Marica

England: Nature Publishing Group UK

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