Advertisement

Acute endurance exercise increases skeletal muscle uncoupling protein-3 gene expression in untrained but not trained humans

  • Robert C. Noland
    Affiliations
    Departments of Exercise and Sport Science (Human Performance Laboratory) and Physiology, Brody School of Medicine, East Carolina University, Greenville, NC; and the Departments of Histopathology and Clinical Biochemistry, Addenbrookes Hospital, Cambridge, United Kingdom
    Search for articles by this author
  • Robert C. Hickner
    Affiliations
    Departments of Exercise and Sport Science (Human Performance Laboratory) and Physiology, Brody School of Medicine, East Carolina University, Greenville, NC; and the Departments of Histopathology and Clinical Biochemistry, Addenbrookes Hospital, Cambridge, United Kingdom
    Search for articles by this author
  • Mercedes Jimenez-Linan
    Affiliations
    Departments of Exercise and Sport Science (Human Performance Laboratory) and Physiology, Brody School of Medicine, East Carolina University, Greenville, NC; and the Departments of Histopathology and Clinical Biochemistry, Addenbrookes Hospital, Cambridge, United Kingdom
    Search for articles by this author
  • Antonio Vidal-Puig
    Affiliations
    Departments of Exercise and Sport Science (Human Performance Laboratory) and Physiology, Brody School of Medicine, East Carolina University, Greenville, NC; and the Departments of Histopathology and Clinical Biochemistry, Addenbrookes Hospital, Cambridge, United Kingdom
    Search for articles by this author
  • Donghai Zheng
    Affiliations
    Departments of Exercise and Sport Science (Human Performance Laboratory) and Physiology, Brody School of Medicine, East Carolina University, Greenville, NC; and the Departments of Histopathology and Clinical Biochemistry, Addenbrookes Hospital, Cambridge, United Kingdom
    Search for articles by this author
  • G.Lynis Dohm
    Affiliations
    Departments of Exercise and Sport Science (Human Performance Laboratory) and Physiology, Brody School of Medicine, East Carolina University, Greenville, NC; and the Departments of Histopathology and Clinical Biochemistry, Addenbrookes Hospital, Cambridge, United Kingdom
    Search for articles by this author
  • Ronald N. Cortright
    Affiliations
    Departments of Exercise and Sport Science (Human Performance Laboratory) and Physiology, Brody School of Medicine, East Carolina University, Greenville, NC; and the Departments of Histopathology and Clinical Biochemistry, Addenbrookes Hospital, Cambridge, United Kingdom
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      In rodents, acute exercise increases skeletal muscle uncoupling protein (UCP) gene expression and is associated with elevations in serum nonesterified fatty acids (NEFA). To test whether contractions increase UCP mRNA levels in humans, vastus lateralis biopsies were obtained 1 hour postexercise from untrained and trained subjects and analyzed for UCP-2 and UCP-3 long (UCP-3L) and short (UCP-3S) isoforms. The acute exercise bout (graded cycling protocol; 65% to 85% relative V̇o2max) induced significant (P <.01) elevations in serum NEFA in both untrained and trained subjects, but the increase in untrained subjects was significantly (P <.05) greater (60% v 30%). Ribonuclease protection assay demonstrated that basal levels of all UCP isoforms measured were similar between the 2 groups. However, acute exercise induced a significant increase (P <.02) in both UCP-3L and UCP-3S, but not UCP-2 mRNA levels in untrained, but not trained subjects. Correlation analysis did not show a significant relationship between exercise-induced changes in NEFA and UCP-3 levels. These results demonstrate that acute endurance exercise increases UCP-3 gene expression only in untrained skeletal muscle, but this effect does not seem to be tightly linked to the exercise-induced fluctuations in serum NEFA levels. Copyright 2003, Elsevier Science (USA). All rights reserved.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Metabolism - Clinical and Experimental
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ricquier D
        • Bouillaud F
        Mitochondrial uncoupling proteins: From mitochondria to the regulation of energy balance.
        J Physiol. 2000; 529: 3-10
        • Garruti G
        • Ricquier D
        Analysis of uncoupling protein and its mRNA in adipose tissue deposits of adult humans.
        Int J Obes Relat Metab Disord. 1992; 16: 383-390
        • Vidal-Puig A
        • Solanes G
        • Grujic D
        • et al.
        UCP3: An uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue.
        Biochem Biophys Res Commun. 1997; 235: 79-82
        • Boss O
        • Samec S
        • Paoloni-Giacobino A
        • et al.
        Uncoupling protein-3: A new member of the mitochondrial carrier family with tissue-specific expression.
        FEBS Lett. 1997; 408: 39-42
        • Fleury C
        • Neverova M
        • Collins S
        • et al.
        Uncoupling protein-2: A novel gene linked to obesity and hyperinsulinemia.
        Nat Genet. 1997; 15: 269-272
        • Gong DW
        • He Y
        • Karas M
        • et al.
        Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin.
        J Biol Chem. 1997; 272: 24129-24132
        • Boss O
        • Samec S
        • Desplanches D
        • et al.
        Effect of endurance training on mRNA expression of uncoupling proteins 1, 2, and 3 in the rat.
        FASEB J. 1998; 12: 335-339
        • Boss O
        • Samec S
        • Kuhne F
        • et al.
        Uncoupling protein-3 expression in rodent skeletal muscle is modulated by food intake but not by changes in environmental temperature.
        J Biol Chem. 1998; 273: 5-8
        • Boss O
        • Hagen T
        • Lowell BB
        Uncoupling proteins 2 and 3: Potential regulators of mitochondrial energy metabolism.
        Diabetes. 2000; 49: 143-156
        • Simoneau JA
        • Kelley DE
        • Warden C
        Obesity and increased contractile activity influence the protein content of UCP2 in human skeletal muscle.
        Int J Obes Relat Metab Disord. 1999; 23: S68-S71
        • Dulloo AG
        • Samec S
        Uncoupling proteins: Do they have a role in body weight regulation?.
        News Physiol Sci. 2000; 15: 313-318
        • Schrauwen P
        • Troost FJ
        • Xia J
        • et al.
        Skeletal muscle UCP2 and UCP3 expression in trained and untrained male subjects.
        Int J Obes Relat Metab Disord. 1999; 23: 966-972
        • Schrauwen P
        • Hesselink MK
        • Vaartjes I
        • et al.
        Effect of acute exercise on uncoupling protein 3 is a fat metabolism-mediated effect.
        Am J Physiol. 2002; 282: E11-E17
        • Cortright RN
        • Zheng D
        • Jones JP
        • et al.
        Regulation of skeletal muscle UCP-2 and UCP-3 gene expression by exercise and denervation.
        Am J Physiol. 1999; 276: E217-E221
        • Tsuboyama-Kasaoka N
        • Tsunoda N
        • Maruyama K
        • et al.
        Up-regulation of uncoupling protein 3 (UCP3) mRNA by exercise training and down-regulation of UCP3 by denervation in skeletal muscles.
        Biochem Biophys Res Commun. 1998; 247: 498-503
        • Zhou M
        • Lin BZ
        • Coughlin S
        • et al.
        UCP-3 expression in skeletal muscle: Effects of exercise, hypoxia, and AMP-activated protein kinase.
        Am J Physiol. 2000; 279: E622-E629
        • Pedersen SB
        • Lund S
        • Buhl ES
        • et al.
        Insulin and contraction directly stimulate UCP2 and UCP3 mRNA expression in rat skeletal muscle in vitro.
        Biochem Biophys Res Commun. 2001; 283: 19-25
        • Pilegaard H
        • Ordway GA
        • Saltin B
        • et al.
        Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise.
        Am J Physiol. 2000; 279: E806-E814
        • Tonkonogi M
        • Krook A
        • Walsh B
        • et al.
        Endurance training increases stimulation of uncoupling of skeletal muscle mitochondria in humans by non-esterified fatty acids: An uncoupling-protein-mediated effect?.
        Biochem J. 2000; 351: 805-810
        • Hjeltnes N
        • Fernstrom M
        • Zierath JR
        • et al.
        Regulation of UCP2 and UCP3 by muscle disuse and physical activity in tetraplegic subjects.
        Diabetologia. 1999; 42: 826-830
        • Himms-Hagen J
        • Harper ME
        Physiological role of UCP3 may be export of fatty acids from mitochondria when fatty acid oxidation predominates: An hypothesis.
        Exp Biol Med. 2001; 226: 78-84
        • Samec S
        • Seydoux J
        • Dulloo AG
        Role of UCP homologues in skeletal muscles and brown adipose tissue: Mediators of thermogenesis or regulators of lipids as fuel substrate?.
        FASEB J. 1998; 12: 715-724
        • Yoshitomi H
        • Yamazaki K
        • Abe S
        • et al.
        Differential regulation of mouse uncoupling proteins among brown adipose tissue, white adipose tissue, and skeletal muscle in chronic beta 3 adrenergic receptor agonist treatment.
        Biochem Biophys Res Commun. 1998; 253: 85-91
        • Weigle DS
        • Selfridge LE
        • Schwartz MW
        • et al.
        Elevated free fatty acids induce uncoupling protein 3 expression in muscle: A potential explanation for the effect of fasting.
        Diabetes. 1998; 47: 298-302
        • Hwang CS
        • Lane MD
        Up-regulation of uncoupling protein-3 by fatty acid in C2C12 myotubes.
        Biochem Biophys Res Commun. 1999; 258: 464-469
        • Khalfallah Y
        • Fages S
        • Laville M
        • et al.
        Regulation of uncoupling protein-2 and uncoupling protein-3 mRNA expression during lipid infusion in human skeletal muscle and subcutaneous adipose tissue.
        Diabetes. 2000; 49: 25-31
        • Muoio DM
        • Dohm GL
        • Fiedorek Jr, FT
        • et al.
        Leptin directly alters lipid partitioning in skeletal muscle.
        Diabetes. 1997; 46: 1360-1363
        • Scarpace PJ
        • Matheny M
        • Pollock BH
        • et al.
        Leptin increases uncoupling protein expression and energy expenditure.
        Am J Physiol. 1997; 273: E226-E230
        • Vidal-Puig AJ
        • Grujic D
        • Zhang CY
        • et al.
        Energy metabolism in uncoupling protein 3 gene knockout mice.
        J Biol Chem. 2000; 275: 16258-16266
        • Korshunov SS
        • Skulachev VP
        • Starkov AA
        High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria.
        FEBS Lett. 1997; 416: 15-18
        • Smith JA
        • Telford RD
        • Mason IB
        • et al.
        Exercise, training and neutrophil microbicidal activity.
        Int J Sports Med. 1990; 11: 179-187
        • Oh-ishi S
        • Kizaki T
        • Ookawara T
        • et al.
        Endurance training improves the resistance of rat diaphragm to exercise-induced oxidative stress.
        Am J Respir Crit Care Med. 1997; 156: 1579-1585
        • Sato H
        • Suzuki K
        • Nakaji S
        • et al.
        Effects of acute endurance exercise and 8 week training on the production of reactive oxygen species from neutrophils in untrained men.
        Nippon Eiseigaku Zasshi. 1998; 53: 431-440
        • Miyazaki H
        • Oh-ishi S
        • Ookawara T
        • et al.
        Strenuous endurance training in humans reduces oxidative stress following exhausting exercise.
        Eur J Appl Physiol. 2001; 84: 1-6
        • Tonkonogi M
        • Sahlin K
        Physical exercise and mitochondrial function in human skeletal muscle.
        Exerc Sport Sci Rev. 2002; 30: 129-137