Matches in SemOpenAlex for { <https://semopenalex.org/work/W4306660742> ?p ?o ?g. }
- W4306660742 abstract "ABSTRACT Lipotoxicity, the accumulation of lipids in non-adipose tissues, alters the metabolic transcriptome and mitochondrial metabolism in skeletal muscle. The mechanisms involved remain poorly understood. Here we show that lipotoxicity increased histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5), which reduced the expression of metabolic genes and oxidative metabolism in skeletal muscle. This metabolic reprogramming was linked with reduced expression of p53 pathway genes that mediate apoptosis and ferroptosis, as well as preserved muscle cell viability in response to lipotoxicity. Mechanistically, increased HDAC4 and 5 decreased acetylation of p53 at K120, a modification required for transcriptional activation of apoptosis, while metabolically sensitive redox drivers of ferroptosis were also reduced. Overexpression of loss-of-function HDAC4 and HDAC5 mutants in skeletal muscle of obese db/db mice enhanced oxidative capacity, increased apoptosis and ferroptosis and reduced muscle mass. This study identifies HDAC4 and HDAC5 as repressors of the oxidative state of skeletal muscle, which is linked to inhibition of cell death pathways and preservation of muscle integrity in response to lipotoxicity." @default.
- W4306660742 created "2022-10-18" @default.
- W4306660742 creator A5007553024 @default.
- W4306660742 creator A5007776919 @default.
- W4306660742 creator A5010188514 @default.
- W4306660742 creator A5014634967 @default.
- W4306660742 creator A5015374873 @default.
- W4306660742 creator A5036754896 @default.
- W4306660742 creator A5041546884 @default.
- W4306660742 creator A5044194965 @default.
- W4306660742 creator A5044803037 @default.
- W4306660742 creator A5045922186 @default.
- W4306660742 creator A5068732085 @default.
- W4306660742 creator A5069061166 @default.
- W4306660742 creator A5070000043 @default.
- W4306660742 creator A5075863673 @default.
- W4306660742 creator A5081707958 @default.
- W4306660742 creator A5090498933 @default.
- W4306660742 date "2022-10-17" @default.
- W4306660742 modified "2023-10-14" @default.
- W4306660742 title "Class IIa HDACs inhibit cell death pathways and protect muscle integrity in response to lipotoxicity" @default.
- W4306660742 cites W1597446425 @default.
- W4306660742 cites W1795417572 @default.
- W4306660742 cites W1900565974 @default.
- W4306660742 cites W1982545065 @default.
- W4306660742 cites W1983702928 @default.
- W4306660742 cites W2001369189 @default.
- W4306660742 cites W2014885180 @default.
- W4306660742 cites W2027670788 @default.
- W4306660742 cites W2032264012 @default.
- W4306660742 cites W2032328453 @default.
- W4306660742 cites W2036834412 @default.
- W4306660742 cites W2038324148 @default.
- W4306660742 cites W2049481764 @default.
- W4306660742 cites W2061104522 @default.
- W4306660742 cites W2065504943 @default.
- W4306660742 cites W2067107606 @default.
- W4306660742 cites W2087944248 @default.
- W4306660742 cites W2096334738 @default.
- W4306660742 cites W2096372899 @default.
- W4306660742 cites W2104872226 @default.
- W4306660742 cites W2109223610 @default.
- W4306660742 cites W2112522013 @default.
- W4306660742 cites W2129736201 @default.
- W4306660742 cites W2154260730 @default.
- W4306660742 cites W2155867875 @default.
- W4306660742 cites W2156613731 @default.
- W4306660742 cites W2170255149 @default.
- W4306660742 cites W2174978286 @default.
- W4306660742 cites W2343839740 @default.
- W4306660742 cites W2497610175 @default.
- W4306660742 cites W2501302813 @default.
- W4306660742 cites W2519704397 @default.
- W4306660742 cites W2522038806 @default.
- W4306660742 cites W2527907612 @default.
- W4306660742 cites W2550324626 @default.
- W4306660742 cites W2742797230 @default.
- W4306660742 cites W2762087180 @default.
- W4306660742 cites W2883879320 @default.
- W4306660742 cites W2918938634 @default.
- W4306660742 cites W3040861037 @default.
- W4306660742 cites W3094589866 @default.
- W4306660742 cites W3123922203 @default.
- W4306660742 cites W4225146432 @default.
- W4306660742 cites W4225919002 @default.
- W4306660742 cites W4308105849 @default.
- W4306660742 doi "https://doi.org/10.1101/2022.10.17.512492" @default.
- W4306660742 hasPublicationYear "2022" @default.
- W4306660742 type Work @default.
- W4306660742 citedByCount "0" @default.
- W4306660742 crossrefType "posted-content" @default.
- W4306660742 hasAuthorship W4306660742A5007553024 @default.
- W4306660742 hasAuthorship W4306660742A5007776919 @default.
- W4306660742 hasAuthorship W4306660742A5010188514 @default.
- W4306660742 hasAuthorship W4306660742A5014634967 @default.
- W4306660742 hasAuthorship W4306660742A5015374873 @default.
- W4306660742 hasAuthorship W4306660742A5036754896 @default.
- W4306660742 hasAuthorship W4306660742A5041546884 @default.
- W4306660742 hasAuthorship W4306660742A5044194965 @default.
- W4306660742 hasAuthorship W4306660742A5044803037 @default.
- W4306660742 hasAuthorship W4306660742A5045922186 @default.
- W4306660742 hasAuthorship W4306660742A5068732085 @default.
- W4306660742 hasAuthorship W4306660742A5069061166 @default.
- W4306660742 hasAuthorship W4306660742A5070000043 @default.
- W4306660742 hasAuthorship W4306660742A5075863673 @default.
- W4306660742 hasAuthorship W4306660742A5081707958 @default.
- W4306660742 hasAuthorship W4306660742A5090498933 @default.
- W4306660742 hasBestOaLocation W43066607421 @default.
- W4306660742 hasConcept C104317684 @default.
- W4306660742 hasConcept C134018914 @default.
- W4306660742 hasConcept C190283241 @default.
- W4306660742 hasConcept C27253355 @default.
- W4306660742 hasConcept C2777391703 @default.
- W4306660742 hasConcept C2778305200 @default.
- W4306660742 hasConcept C2779306644 @default.
- W4306660742 hasConcept C2779959927 @default.
- W4306660742 hasConcept C31573885 @default.
- W4306660742 hasConcept C44353895 @default.
- W4306660742 hasConcept C55493867 @default.
- W4306660742 hasConcept C58793620 @default.