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The Chicken Ovalbumin Upstream Promoter-Transcription Factors Modulate Genes and Pathways Involved in Skeletal Muscle Cell Metabolism

journal contribution
posted on 2023-05-18, 10:34 authored by Stephen MyersStephen Myers, Wang, S-C M, Muscat, GEO
The chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) are "orphan" members of the nuclear hormone receptor (NR) superfamily. COUP-TFs are involved in organogenesis and neurogenesis. However, their role in skeletal muscle (and other major mass tissues) and metabolism remains obscure. Skeletal muscle accounts for ~40% of total body mass and energy expenditure. Moreover, this peripheral tissue is a primary site of glucose and fatty acid utilization. We utilize small interfering RNA (siRNA)-mediated attenuation of CoupTfI and II (mRNA and protein) in a skeletal muscle cell culture model to understand the regulatory role of Coup-Tfs in this energy demanding tissue. This targeted NR repression resulted in the significant attenuation of genes that regulate lipid mobilization and utilization (including Ppara, Fabp3, and Cpt-1). This was coupled to reduced fatty acid -oxidation. Additionally we observed significant attenuation of Ucp1, a gene involved in energy expenditure. Concordantly, we observed a 5-fold increase in ATP levels in cells with siRNA-mediated repression of Coup-TfI and II. Furthermore, the expression of "classical" liver X receptor (LXR) target genes involved in reverse cholesterol transport (Abca1 and Abcg1) were both significantly repressed. Moreover, we observed that repression of the Coup-Tfs ablated the activation of Abca1, and Abcg1 mRNA expression by the selective LXR agonist, T0901317. In concordance, Coup-TfsiRNA-transfected cells were refractory toLxr-mediated reduction of total intracellular cholesterol levels in contrast to the negative control cells. In agreement Lxr-mediated activation of the Abca1 promoter in Coup-Tf-siRNA cells was attenuated. Collectively, these data suggest a pivotal role for Coup-Tfs in the regulation of lipid utilization/cholesterol homeostasis in skeletal muscle cells and the modulation of Lxr-dependent gene regulation.


Publication title

Journal of Biological Chemistry






24149 -24160




School of Nursing


Amer Soc Biochemistry Molecular Biology Inc

Place of publication

9650 Rockville Pike, Bethesda, USA, Md, 20814-3996

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© 2006 by The American Society for Biochemistry and Molecular Biology

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Clinical health not elsewhere classified

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