Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity

Keith Baar, Zheng Song, Clay F. Semenkovich, Terry E. Jones, Dong-Ho Han, Lorraine A. Nolte, Edward O. Ojuka, May Chen, John O. Holloszy

    Research output: Contribution to journalArticle

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    Abstract

    Nuclear respiratory factor 1 (NRF-1) is a transcriptional activator of nuclear genes that encode a range of mitochondrial proteins including cytochrome c, various other respiratory chain subunits, and d-aminolevulinate synthase. Activation of NRF-1 in fibroblasts has been shown to induce increases in cytochrome c expression and mitochondrial respiratory capacity. To further evaluate the role of NRF-1 in the regulation of mitochondrial biogenesis and respiratory capacity, we generated transgenic mice overexpressing NRF-1 in skeletal muscle. Cytochrome c expression was increased ~twofold and d-aminolevulinate synthase was increased ~50% in NRF-1 transgenic muscle. The levels of some mitochondrial proteins were increased 50–60%, while others were unchanged. Muscle respiratory capacity was not increased in the NRF-1 transgenic mice. A finding that provides new insight regarding the role of NRF-1 was that expression of MEF2A and GLUT4 was increased in NRF-1 transgenic muscle. The increase in GLUT4 was associated with a proportional increase in insulin-stimulated glucose transport. These results show that an isolated increase in NRF-1 is not sufficient to bring about a coordinated increase in expression of all of the proteins necessary for assembly of functional mitochondria. They also provide the new information that NRF-1 overexpression results in increased expression of GLUT4.—Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E,. Han, D.-H., Nolte, L. A., Ojuka, E. O., Chen, M., Holloszy, J. O. Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity.
    Original languageEnglish
    Pages (from-to)1666-1673
    Number of pages8
    JournalFASEB Journal
    Volume17
    Issue number12
    DOIs
    Publication statusPublished - Sep 2003

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    Nuclear Respiratory Factor 1
    Muscle
    Skeletal Muscle
    Glucose
    Cytochromes c
    Mitochondrial Proteins
    Transgenic Mice
    Muscles
    Respiratory Muscles
    Mitochondria
    Organelle Biogenesis
    Fibroblasts
    Music
    Electron Transport

    Keywords

    • Respiratory enzymes
    • Mitochondria
    • Cytochrome c
    • Protein synthesis

    Cite this

    Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E., Han, D-H., Nolte, L. A., ... Holloszy, J. O. (2003). Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. FASEB Journal, 17(12), 1666-1673. https://doi.org/10.1096/fj.03-0049com
    Baar, Keith ; Song, Zheng ; Semenkovich, Clay F. ; Jones, Terry E. ; Han, Dong-Ho ; Nolte, Lorraine A. ; Ojuka, Edward O. ; Chen, May ; Holloszy, John O. / Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. In: FASEB Journal. 2003 ; Vol. 17, No. 12. pp. 1666-1673.
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    abstract = "Nuclear respiratory factor 1 (NRF-1) is a transcriptional activator of nuclear genes that encode a range of mitochondrial proteins including cytochrome c, various other respiratory chain subunits, and d-aminolevulinate synthase. Activation of NRF-1 in fibroblasts has been shown to induce increases in cytochrome c expression and mitochondrial respiratory capacity. To further evaluate the role of NRF-1 in the regulation of mitochondrial biogenesis and respiratory capacity, we generated transgenic mice overexpressing NRF-1 in skeletal muscle. Cytochrome c expression was increased ~twofold and d-aminolevulinate synthase was increased ~50{\%} in NRF-1 transgenic muscle. The levels of some mitochondrial proteins were increased 50–60{\%}, while others were unchanged. Muscle respiratory capacity was not increased in the NRF-1 transgenic mice. A finding that provides new insight regarding the role of NRF-1 was that expression of MEF2A and GLUT4 was increased in NRF-1 transgenic muscle. The increase in GLUT4 was associated with a proportional increase in insulin-stimulated glucose transport. These results show that an isolated increase in NRF-1 is not sufficient to bring about a coordinated increase in expression of all of the proteins necessary for assembly of functional mitochondria. They also provide the new information that NRF-1 overexpression results in increased expression of GLUT4.—Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E,. Han, D.-H., Nolte, L. A., Ojuka, E. O., Chen, M., Holloszy, J. O. Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity.",
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    Baar, K, Song, Z, Semenkovich, CF, Jones, TE, Han, D-H, Nolte, LA, Ojuka, EO, Chen, M & Holloszy, JO 2003, 'Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity', FASEB Journal, vol. 17, no. 12, pp. 1666-1673. https://doi.org/10.1096/fj.03-0049com

    Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. / Baar, Keith; Song, Zheng; Semenkovich, Clay F.; Jones, Terry E.; Han, Dong-Ho; Nolte, Lorraine A.; Ojuka, Edward O.; Chen, May; Holloszy, John O.

    In: FASEB Journal, Vol. 17, No. 12, 09.2003, p. 1666-1673.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity

    AU - Baar, Keith

    AU - Song, Zheng

    AU - Semenkovich, Clay F.

    AU - Jones, Terry E.

    AU - Han, Dong-Ho

    AU - Nolte, Lorraine A.

    AU - Ojuka, Edward O.

    AU - Chen, May

    AU - Holloszy, John O.

    N1 - dc.publisher: Federation of American Societies for Experimental Biology (FASEB)

    PY - 2003/9

    Y1 - 2003/9

    N2 - Nuclear respiratory factor 1 (NRF-1) is a transcriptional activator of nuclear genes that encode a range of mitochondrial proteins including cytochrome c, various other respiratory chain subunits, and d-aminolevulinate synthase. Activation of NRF-1 in fibroblasts has been shown to induce increases in cytochrome c expression and mitochondrial respiratory capacity. To further evaluate the role of NRF-1 in the regulation of mitochondrial biogenesis and respiratory capacity, we generated transgenic mice overexpressing NRF-1 in skeletal muscle. Cytochrome c expression was increased ~twofold and d-aminolevulinate synthase was increased ~50% in NRF-1 transgenic muscle. The levels of some mitochondrial proteins were increased 50–60%, while others were unchanged. Muscle respiratory capacity was not increased in the NRF-1 transgenic mice. A finding that provides new insight regarding the role of NRF-1 was that expression of MEF2A and GLUT4 was increased in NRF-1 transgenic muscle. The increase in GLUT4 was associated with a proportional increase in insulin-stimulated glucose transport. These results show that an isolated increase in NRF-1 is not sufficient to bring about a coordinated increase in expression of all of the proteins necessary for assembly of functional mitochondria. They also provide the new information that NRF-1 overexpression results in increased expression of GLUT4.—Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E,. Han, D.-H., Nolte, L. A., Ojuka, E. O., Chen, M., Holloszy, J. O. Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity.

    AB - Nuclear respiratory factor 1 (NRF-1) is a transcriptional activator of nuclear genes that encode a range of mitochondrial proteins including cytochrome c, various other respiratory chain subunits, and d-aminolevulinate synthase. Activation of NRF-1 in fibroblasts has been shown to induce increases in cytochrome c expression and mitochondrial respiratory capacity. To further evaluate the role of NRF-1 in the regulation of mitochondrial biogenesis and respiratory capacity, we generated transgenic mice overexpressing NRF-1 in skeletal muscle. Cytochrome c expression was increased ~twofold and d-aminolevulinate synthase was increased ~50% in NRF-1 transgenic muscle. The levels of some mitochondrial proteins were increased 50–60%, while others were unchanged. Muscle respiratory capacity was not increased in the NRF-1 transgenic mice. A finding that provides new insight regarding the role of NRF-1 was that expression of MEF2A and GLUT4 was increased in NRF-1 transgenic muscle. The increase in GLUT4 was associated with a proportional increase in insulin-stimulated glucose transport. These results show that an isolated increase in NRF-1 is not sufficient to bring about a coordinated increase in expression of all of the proteins necessary for assembly of functional mitochondria. They also provide the new information that NRF-1 overexpression results in increased expression of GLUT4.—Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E,. Han, D.-H., Nolte, L. A., Ojuka, E. O., Chen, M., Holloszy, J. O. Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity.

    KW - Respiratory enzymes

    KW - Mitochondria

    KW - Cytochrome c

    KW - Protein synthesis

    U2 - 10.1096/fj.03-0049com

    DO - 10.1096/fj.03-0049com

    M3 - Article

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    SP - 1666

    EP - 1673

    JO - FASEB Journal

    JF - FASEB Journal

    SN - 0892-6638

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    ER -