biostudies-literatureLangley MRNCATS NIH HHSNational Multiple Sclerosis SocietyNIDDK NIH HHSEugene and Marcia Applebaum FoundationMayo ClinicNINDS NIH HHSMinnesota State Spinal Cord Injury and Traumatic Brain Injury Research ProgramCraig H. Neilsen Foundation165630https://www.ebi.ac.uk/biostudies/studies/S-EPMC7982965biostudies-literatureUnknown1866(3)Metabolic syndrome is a key risk factor and co-morbidity in multiple sclerosis (MS) and other neurological conditions, such that a better understanding of how a high fat diet contributes to oligodendrocyte loss and the capacity for myelin regeneration has the potential to highlight new treatment targets. Results demonstrate that modeling metabolic dysfunction in mice with chronic high fat diet (HFD) consumption promotes loss of oligodendrocyte progenitors across the brain and spinal cord. A number of transcriptomic and metabolomic changes in ER stress, mitochondrial dysfunction, and oxidative stress pathways in HFD-fed mouse spinal cords were also identified. Moreover, deficits in TCA cycle intermediates and mitochondrial respiration were observed in the chronic HFD spinal cord tissue. OliBiochimica et biophysica acta. Molecular basis of diseaseHigh fat diet consumption results in mitochondrial dysfunction, oxidative stress, and oligodendrocyte loss in the central nervous system.PMC7982965UL1TR000135R01 NS120877RG4958R01NS052741UL1 TR000135R01 NS052741U24 DK100469U24DK100469Scarisbrick IAYoon HKim HNChoi CILangley MRMatveyenko ALeBrasseur NKLanza IRSimon WKleppe LfalseHigh fat diet consumption results in mitochondrial dysfunction, oxidative stress, and oligodendrocyte loss in the central nervous system.Metabolic syndrome is a key risk factor and co-morbidity in multiple sclerosis (MS) and other neurological conditions, such that a better understanding of how a high fat diet contributes to oligodendrocyte loss and the capacity for myelin regeneration has the potential to highlight new treatment targets. Results demonstrate that modeling metabolic dysfunction in mice with chronic high fat diet (HFD) consumption promotes loss of oligodendrocyte progenitors across the brain and spinal cord. A number of transcriptomic and metabolomic changes in ER stress, mitochondrial dysfunction, and oxidative stress pathways in HFD-fed mouse spinal cords were also identified. Moreover, deficits in TCA cycle intermediates and mitochondrial respiration were observed in the chronic HFD spinal cord tissue. Oli2020-01-01T00:00:00Z2020 Mar2026-04-13T03:12:42.533Z2025-02-19T02:12:58.342ZS-EPMC79829653181644010.1016/j.bbadis.2019.165630