Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse

Patrick T. Fueger, Jane Shearer, Tess M. Krueger, Kelly A. Posey, Deanna P. Bracy, Sami Heikkinen, Markku Laakso, Jeffrey N. Rottman, David H. Wasserman

Research output: Contribution to journalArticle

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Abstract

Hexokinase (HK) II content is elevated in fatigue resistant muscle fibres and exercise trained muscle. The aim of this study was to determine if exercise capacity is dependent on muscle HK protein content. C57Bl/6 mice with a 50% HK knockout (HK+/-), no genetic manipulation (wild-type, WT) and an ∼3-fold HK overexpression (HKTg) were tested. Mice (n = 12/group) completed both a maximal oxygen consumption (V̇O2,max) test and an endurance capacity test (run at ∼75% V̇O2,max) on an enclosed treadmill equipped to measure gas exchange. Arterial and venous catheters were surgically implanted into separate groups of mice (n = 9-11/group) in order to measure an index of muscle glucose uptake (Rg) during 30 min of treadmill exercise. Maximum work rate (0.95 ± 0.05, 1.00 ± 0.04 and 1.06 ± 0.07 kg m min-1), V̇O2,max (137 ± 3, 141 ± 4 and 141 ± 5 ml kg-1 min-1) and maximal respiratory exchange ratio (1.04 ± 0.02, 1.00 ± 0.03 and 1.04 ± 0.04) were similar in HK+/-, WT and HKTg, respectively. Exercise endurance capacity (measured as time to exhaustion) increased as HK content increased (55 ± 11, 77 ± 5 and 98 ± 9 min) and this was related to Rg measured in mice during 30 min of exercise (13 ± 2, 24 ± 5 and 42 ± 5 μmol (100 g)-1 min-1). Muscle glycogen in sedentary HK+/- mice and HK+/- mice following 30 min of exercise were significantly lower than in HKTg and WT mice. However, the net exercise-induced muscle glycogen breakdown was equal in the three genotypes. In summary, HK protein content within the range studied (a) was not associated with a difference in the capacity to perform maximal intensity exercise, (b) was a powerful determinant of the ability to sustain moderate intensity exercise, as reducing HK content impaired endurance and increasing HK content enhanced endurance, and (c) although directly related to exercise endurance, was not a determinant of net muscle glycogen usage during exercise. In conclusion, adaptations that increase HK protein content and/or functional activity such as regular exercise contribute to increased muscular endurance.

Original languageEnglish (US)
Pages (from-to)533-541
Number of pages9
JournalJournal of Physiology
Volume566
Issue number2
DOIs
StatePublished - Jul 15 2005
Externally publishedYes

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Hexokinase
Proteins
Muscles
Glycogen
Muscle Fatigue
Muscle Proteins
Oxygen Consumption
Catheters

ASJC Scopus subject areas

  • Physiology

Cite this

Fueger, P. T., Shearer, J., Krueger, T. M., Posey, K. A., Bracy, D. P., Heikkinen, S., ... Wasserman, D. H. (2005). Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse. Journal of Physiology, 566(2), 533-541. https://doi.org/10.1113/jphysiol.2005.085043

Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse. / Fueger, Patrick T.; Shearer, Jane; Krueger, Tess M.; Posey, Kelly A.; Bracy, Deanna P.; Heikkinen, Sami; Laakso, Markku; Rottman, Jeffrey N.; Wasserman, David H.

In: Journal of Physiology, Vol. 566, No. 2, 15.07.2005, p. 533-541.

Research output: Contribution to journalArticle

Fueger, PT, Shearer, J, Krueger, TM, Posey, KA, Bracy, DP, Heikkinen, S, Laakso, M, Rottman, JN & Wasserman, DH 2005, 'Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse', Journal of Physiology, vol. 566, no. 2, pp. 533-541. https://doi.org/10.1113/jphysiol.2005.085043
Fueger PT, Shearer J, Krueger TM, Posey KA, Bracy DP, Heikkinen S et al. Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse. Journal of Physiology. 2005 Jul 15;566(2):533-541. https://doi.org/10.1113/jphysiol.2005.085043
Fueger, Patrick T. ; Shearer, Jane ; Krueger, Tess M. ; Posey, Kelly A. ; Bracy, Deanna P. ; Heikkinen, Sami ; Laakso, Markku ; Rottman, Jeffrey N. ; Wasserman, David H. / Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse. In: Journal of Physiology. 2005 ; Vol. 566, No. 2. pp. 533-541.
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abstract = "Hexokinase (HK) II content is elevated in fatigue resistant muscle fibres and exercise trained muscle. The aim of this study was to determine if exercise capacity is dependent on muscle HK protein content. C57Bl/6 mice with a 50{\%} HK knockout (HK+/-), no genetic manipulation (wild-type, WT) and an ∼3-fold HK overexpression (HKTg) were tested. Mice (n = 12/group) completed both a maximal oxygen consumption (V̇O2,max) test and an endurance capacity test (run at ∼75{\%} V̇O2,max) on an enclosed treadmill equipped to measure gas exchange. Arterial and venous catheters were surgically implanted into separate groups of mice (n = 9-11/group) in order to measure an index of muscle glucose uptake (Rg) during 30 min of treadmill exercise. Maximum work rate (0.95 ± 0.05, 1.00 ± 0.04 and 1.06 ± 0.07 kg m min-1), V̇O2,max (137 ± 3, 141 ± 4 and 141 ± 5 ml kg-1 min-1) and maximal respiratory exchange ratio (1.04 ± 0.02, 1.00 ± 0.03 and 1.04 ± 0.04) were similar in HK+/-, WT and HKTg, respectively. Exercise endurance capacity (measured as time to exhaustion) increased as HK content increased (55 ± 11, 77 ± 5 and 98 ± 9 min) and this was related to Rg measured in mice during 30 min of exercise (13 ± 2, 24 ± 5 and 42 ± 5 μmol (100 g)-1 min-1). Muscle glycogen in sedentary HK+/- mice and HK+/- mice following 30 min of exercise were significantly lower than in HKTg and WT mice. However, the net exercise-induced muscle glycogen breakdown was equal in the three genotypes. In summary, HK protein content within the range studied (a) was not associated with a difference in the capacity to perform maximal intensity exercise, (b) was a powerful determinant of the ability to sustain moderate intensity exercise, as reducing HK content impaired endurance and increasing HK content enhanced endurance, and (c) although directly related to exercise endurance, was not a determinant of net muscle glycogen usage during exercise. In conclusion, adaptations that increase HK protein content and/or functional activity such as regular exercise contribute to increased muscular endurance.",
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