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PGC-1{alpha} is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle.
Am J Physiol Endocrinol Metab. 2010 Sep; 299(3):E456-65.AJ

Abstract

We tested the hypothesis that repeated activation of AMP-activated protein kinase (AMPK) induces mitochondrial and glucose membrane transporter mRNA/protein expression via a peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)-dependent mechanism. Whole body PGC-1alpha-knockout (KO) and littermate wild-type (WT) mice were given either single or repeated subcutaneous injections of the AMPK activator AICAR or saline. Skeletal muscles were removed either 1 or 4 h after the single AICAR treatment or 24 h after the last injection following repeated AICAR treatment. Repeated AICAR treatment increased GLUT4, cytochrome (cyt) c oxidase I, and (cyt) c protein expression approximately 10-40% relative to saline in white muscles of WT but not of PGC-1alpha-KO mice, whereas fatty acid translocase/CD36 (FAT/CD36) protein expression was unaffected by AICAR treatment in both genotypes. GLUT4, cyt c, and FAT/CD36 mRNA content increased 30-60% 4 h after a single AICAR injection relative to saline in WT, and FAT/CD36 mRNA content decreased in PGC-1alpha-KO mice. One hour after a single AICAR treatment, phosphorylation of AMPK and the downstream target acetyl-coenzyme A carboxylase increased in all muscles investigated independent of genotype, indicating normal AICAR-induced AMPK signaling in the absence of PGC-1alpha. The hexokinase II (HKII) mRNA and protein response was similar in muscles of WT and PGC-1alpha-KO mice after single and repeated AICAR treatments, respectively, confirming that HKII is regulated independently of PGC-1alpha in response to AICAR. In conclusion, here we provide genetic evidence for a role of PGC-1alpha in AMPK-mediated regulation of mitochondrial and glucose membrane transport protein expression in skeletal muscle.

Authors+Show Affiliations

Centre of Inflammation and Metabolism and Copenhagen Muscle Research Centre, Department of Biology, Univ. of Copenhagen, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20628026

Citation

Leick, Lotte, et al. "PGC-1{alpha} Is Required for AICAR-induced Expression of GLUT4 and Mitochondrial Proteins in Mouse Skeletal Muscle." American Journal of Physiology. Endocrinology and Metabolism, vol. 299, no. 3, 2010, pp. E456-65.
Leick L, Fentz J, Biensø RS, et al. PGC-1{alpha} is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle. Am J Physiol Endocrinol Metab. 2010;299(3):E456-65.
Leick, L., Fentz, J., Biensø, R. S., Knudsen, J. G., Jeppesen, J., Kiens, B., Wojtaszewski, J. F., & Pilegaard, H. (2010). PGC-1{alpha} is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle. American Journal of Physiology. Endocrinology and Metabolism, 299(3), E456-65. https://doi.org/10.1152/ajpendo.00648.2009
Leick L, et al. PGC-1{alpha} Is Required for AICAR-induced Expression of GLUT4 and Mitochondrial Proteins in Mouse Skeletal Muscle. Am J Physiol Endocrinol Metab. 2010;299(3):E456-65. PubMed PMID: 20628026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PGC-1{alpha} is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle. AU - Leick,Lotte, AU - Fentz,Joachim, AU - Biensø,Rasmus S, AU - Knudsen,Jakob G, AU - Jeppesen,Jacob, AU - Kiens,Bente, AU - Wojtaszewski,Jørgen F P, AU - Pilegaard,Henriette, Y1 - 2010/07/13/ PY - 2010/7/15/entrez PY - 2010/7/16/pubmed PY - 2010/10/7/medline SP - E456 EP - 65 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 299 IS - 3 N2 - We tested the hypothesis that repeated activation of AMP-activated protein kinase (AMPK) induces mitochondrial and glucose membrane transporter mRNA/protein expression via a peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)-dependent mechanism. Whole body PGC-1alpha-knockout (KO) and littermate wild-type (WT) mice were given either single or repeated subcutaneous injections of the AMPK activator AICAR or saline. Skeletal muscles were removed either 1 or 4 h after the single AICAR treatment or 24 h after the last injection following repeated AICAR treatment. Repeated AICAR treatment increased GLUT4, cytochrome (cyt) c oxidase I, and (cyt) c protein expression approximately 10-40% relative to saline in white muscles of WT but not of PGC-1alpha-KO mice, whereas fatty acid translocase/CD36 (FAT/CD36) protein expression was unaffected by AICAR treatment in both genotypes. GLUT4, cyt c, and FAT/CD36 mRNA content increased 30-60% 4 h after a single AICAR injection relative to saline in WT, and FAT/CD36 mRNA content decreased in PGC-1alpha-KO mice. One hour after a single AICAR treatment, phosphorylation of AMPK and the downstream target acetyl-coenzyme A carboxylase increased in all muscles investigated independent of genotype, indicating normal AICAR-induced AMPK signaling in the absence of PGC-1alpha. The hexokinase II (HKII) mRNA and protein response was similar in muscles of WT and PGC-1alpha-KO mice after single and repeated AICAR treatments, respectively, confirming that HKII is regulated independently of PGC-1alpha in response to AICAR. In conclusion, here we provide genetic evidence for a role of PGC-1alpha in AMPK-mediated regulation of mitochondrial and glucose membrane transport protein expression in skeletal muscle. SN - 1522-1555 UR - https://www.unboundmedicine.com/medline/citation/20628026/PGC_1{alpha}_is_required_for_AICAR_induced_expression_of_GLUT4_and_mitochondrial_proteins_in_mouse_skeletal_muscle_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00648.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -