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Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle.

Abstract

Clenbuterol, a β2-adrenergic agonist, reduces mitochondrial content and enzyme activities in skeletal muscle, but the mechanism involved has yet to be identified. We examined whether clenbuterol-induced changes in the muscles' metabolic profile and the intrinsic capacity of mitochondria to oxidize substrates are associated with reductions in the nuclear receptor coactivator PGC-1 alpha and/or an increase in the nuclear corepressor RIP140. In rats, clenbuterol was provided in the drinking water (30 mg/l). In 3 wk, this increased body (8%) and muscle weights (12-17%). In red (R) and white (W) muscles, clenbuterol induced reductions in mitochondrial content (citrate synthase: R, 27%; W, 52%; cytochrome-c oxidase: R, 24%; W, 34%), proteins involved in fatty acid transport (fatty acid translocase/CD36: R, 36%; W, 35%) and oxidation [β-hydroxyacyl CoA dehydrogenase (β-HAD): R, 33%; W, 62%], glucose transport (GLUT4: R, 8%; W, 13%), lactate transport monocarboxylate transporter (MCT1: R, 61%; W, 37%), and pyruvate oxidation (PDHE1α, R, 18%; W, 12%). Concurrently, only red muscle lactate dehydrogenase activity (25%) and MCT4 (31%) were increased. Palmitate oxidation was reduced in subsarcolemmal (SS) (R, 30%; W, 52%) and intermyofibrillar (IMF) mitochondria (R, 17%; W, 44%) along with reductions in β-HAD activity (SS: R, 17%; W, 51%; IMF: R, 20%; W, 57%). Pyruvate oxidation was only reduced in SS mitochondria (R, 20%; W, 28%), but this was not attributable solely to PDHE1α, which was reduced in both SS (R, 21%; W, 20%) and IMF mitochondria (R, 15%; W, 43%). These extensive metabolic changes induced by clenbuterol were associated with reductions in PGC-1α (R, 37%; W, 32%) and increases in RIP140 (R, 23%; W, 21%). This is the first evidence that clenbuterol appears to exert its metabolic effects via simultaneous and reciprocal changes in the nuclear receptor coactivator PGC-1α and the nuclear corepressor RIP140.

Authors+Show Affiliations

Department of Sports Sciences, The University of Tokyo, Japan.No 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

22071161

Citation

Hoshino, Daisuke, et al. "Clenbuterol, a Β2-adrenergic Agonist, Reciprocally Alters PGC-1 Alpha and RIP140 and Reduces Fatty Acid and Pyruvate Oxidation in Rat Skeletal Muscle." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 302, no. 3, 2012, pp. R373-84.
Hoshino D, Yoshida Y, Holloway GP, et al. Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2012;302(3):R373-84.
Hoshino, D., Yoshida, Y., Holloway, G. P., Lally, J., Hatta, H., & Bonen, A. (2012). Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 302(3), pp. R373-84. doi:10.1152/ajpregu.00183.2011.
Hoshino D, et al. Clenbuterol, a Β2-adrenergic Agonist, Reciprocally Alters PGC-1 Alpha and RIP140 and Reduces Fatty Acid and Pyruvate Oxidation in Rat Skeletal Muscle. Am J Physiol Regul Integr Comp Physiol. 2012 Feb 1;302(3):R373-84. PubMed PMID: 22071161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle. AU - Hoshino,Daisuke, AU - Yoshida,Yuko, AU - Holloway,Graham P, AU - Lally,James, AU - Hatta,Hideo, AU - Bonen,Arend, Y1 - 2011/11/09/ PY - 2011/11/11/entrez PY - 2011/11/11/pubmed PY - 2012/4/20/medline SP - R373 EP - 84 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am. J. Physiol. Regul. Integr. Comp. Physiol. VL - 302 IS - 3 N2 - Clenbuterol, a β2-adrenergic agonist, reduces mitochondrial content and enzyme activities in skeletal muscle, but the mechanism involved has yet to be identified. We examined whether clenbuterol-induced changes in the muscles' metabolic profile and the intrinsic capacity of mitochondria to oxidize substrates are associated with reductions in the nuclear receptor coactivator PGC-1 alpha and/or an increase in the nuclear corepressor RIP140. In rats, clenbuterol was provided in the drinking water (30 mg/l). In 3 wk, this increased body (8%) and muscle weights (12-17%). In red (R) and white (W) muscles, clenbuterol induced reductions in mitochondrial content (citrate synthase: R, 27%; W, 52%; cytochrome-c oxidase: R, 24%; W, 34%), proteins involved in fatty acid transport (fatty acid translocase/CD36: R, 36%; W, 35%) and oxidation [β-hydroxyacyl CoA dehydrogenase (β-HAD): R, 33%; W, 62%], glucose transport (GLUT4: R, 8%; W, 13%), lactate transport monocarboxylate transporter (MCT1: R, 61%; W, 37%), and pyruvate oxidation (PDHE1α, R, 18%; W, 12%). Concurrently, only red muscle lactate dehydrogenase activity (25%) and MCT4 (31%) were increased. Palmitate oxidation was reduced in subsarcolemmal (SS) (R, 30%; W, 52%) and intermyofibrillar (IMF) mitochondria (R, 17%; W, 44%) along with reductions in β-HAD activity (SS: R, 17%; W, 51%; IMF: R, 20%; W, 57%). Pyruvate oxidation was only reduced in SS mitochondria (R, 20%; W, 28%), but this was not attributable solely to PDHE1α, which was reduced in both SS (R, 21%; W, 20%) and IMF mitochondria (R, 15%; W, 43%). These extensive metabolic changes induced by clenbuterol were associated with reductions in PGC-1α (R, 37%; W, 32%) and increases in RIP140 (R, 23%; W, 21%). This is the first evidence that clenbuterol appears to exert its metabolic effects via simultaneous and reciprocal changes in the nuclear receptor coactivator PGC-1α and the nuclear corepressor RIP140. SN - 1522-1490 UR - https://www.unboundmedicine.com/medline/citation/22071161/Clenbuterol_a_β2_adrenergic_agonist_reciprocally_alters_PGC_1_alpha_and_RIP140_and_reduces_fatty_acid_and_pyruvate_oxidation_in_rat_skeletal_muscle_ L2 - http://www.physiology.org/doi/full/10.1152/ajpregu.00183.2011?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -