Abstract
Aim/hypothesis:
The aim of this study was to investigate mitochondrial function, fibre-type distribution and substrate oxidation during exercise in arm and leg muscles in male postobese (PO), obese (O) and age- and body mass index (BMI)-matched control (C) subjects. The hypothesis of the study was that fat oxidation during exercise might be differentially preserved in leg and arm muscles after weight loss.
Methods:
Indirect calorimetry was used to calculate fat and carbohydrate oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle biopsy samples were obtained from musculus deltoideus (m. deltoideus) and m. vastus lateralis muscles. Fibre-type composition, enzyme activity and O2 flux capacity of saponin-permeabilized muscle fibres were measured, the latter by high-resolution respirometry.
Results:
During the graded exercise tests, peak fat oxidation during leg cycling and the relative workload at which it occurred (FatMax) were higher in PO and O than in C. During arm cranking, peak fat oxidation was higher in O than in C, and FatMax was higher in O than in PO and C. Similar fibre-type composition was found between groups. Plasma adiponectin was higher in PO than in C and O, and plasma leptin was higher in O than in PO and C.
Conclusions:
In O subjects, maximal fat oxidation during exercise and the eliciting relative exercise intensity are increased. This is associated with higher intramuscular triglyceride levels and higher resting non esterified fatty acid (NEFA) concentrations, but not with differences in fibre-type composition, mitochondrial function or muscle enzyme levels compared with Cs. In PO subjects, the changes in fat oxidation are preserved during leg, but not during arm, exercise.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Holloszy JO, Kohrt WM, Hansen PA . The regulation of carbohydrate and fat metabolism during and after exercise. Front Biosci 1998; 3: D1011–D1027.
Kelley DE, Goodpaster B, Wing RR, Simoneau JA . Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol 1999; 277 (6 Part 1): E1130–E1141.
Kim JY, Hickner RC, Cortright RL, Dohm GL, Houmard JA . Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol 2000; 279: E1039–E1044.
Perez-Martin A, Dumortier M, Raynaud E, Brun JF, Fedou C, Bringer J et al. Balance of substrate oxidation during submaximal exercise in lean and obese people. Diabetes Metab 2001; 27 (4 Part 1): 466–474.
Simoneau JA, Veerkamp JH, Turcotte LP, Kelley DE . Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss. FASEB J 1999; 13: 2051–2060.
Thyfault JP, Kraus RM, Hickner RC, Howell AW, Wolfe RR, Dohm GL . Impaired plasma fatty acid oxidation in extremely obese women. Am J Physiol Endocrinol Metab 2004; 287: E1076–E1081.
Goodpaster BH, Wolfe RR, Kelley DE . Effects of obesity on substrate utilization during exercise. Obes Res 2002; 10: 575–584.
Kanaley JA, Cryer PE, Jensen MD . Fatty acid kinetic responses to exercise. Effects of obesity, body fat distribution, and energy-restricted diet. J Clin Invest 1993; 92: 255–261.
Fuentes T, Ara I, Guadalupe-Grau A, Larsen S, Stallknecht B, Olmedillas H et al. Leptin receptor 170 KDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance. Exp Physiol 2010; 95: 160–171.
Hojlund K, Mogensen M, Sahlin K, Beck-Nielsen H . Mitochondrial dysfunction in type 2 diabetes and obesity. Endocrinol Metab Clin North Am 2008; 37: 713–731, x.
Kelley DE, He J, Menshikova EV, Ritov VB . Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 2002; 51: 2944–2950.
Mogensen M, Sahlin K, Fernstrom M, Glintborg D, Vind BF, Beck-Nielsen H et al. Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 2007; 56: 1592–1599.
Larsen S, Ara I, Rabol R, Andersen JL, Boushel R, Dela F et al. Are substrate use during exercise and mitochondrial respiratory capacity decreased in arm and leg muscle in type 2 diabetes? Diabetologia 2009; 52: 1400–1408.
Menshikova EV, Ritov VB, Toledo FG, Ferrell RE, Goodpaster BH, Kelley DE . Effects of weight loss and physical activity on skeletal muscle mitochondrial function in obesity. Am J Physiol Endocrinol Metab 2005; 288: E818–E825.
Greco AV, Mingrone G, Giancaterini A, Manco M, Morroni M, Cinti S et al. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes 2002; 51: 144–151.
Kempen KP, Saris WH, Kuipers H, Glatz JF, Van DV . Skeletal muscle metabolic characteristics before and after energy restriction in human obesity: fibre type, enzymatic beta-oxidative capacity and fatty acid-binding protein content. Eur J Clin Invest 1998; 28: 1030–1037.
Raben A, Mygind E, Astrup A . Lower activity of oxidative key enzymes and smaller fiber areas in skeletal muscle of postobese women. Am J Physiol Endocrinol 1998; 38: E487–E494.
Olsen DB, Sacchetti M, Dela F, Ploug T, Saltin B . Glucose clearance is higher in arm than leg muscle in type 2 diabetes. J Physiol 2005; 565 (Part 2): 555–562.
Reynolds TH, Supiano MA, Dengel DR . Regional differences in glucose clearance: effects of insulin and resistance training on arm and leg glucose clearance in older hypertensive individuals. J Appl Physiol 2007; 102: 985–991.
Sacchetti M, Olsen DB, Saltin B, van Hall G . Heterogeneity in limb fatty acid kinetics in type 2 diabetes. Diabetologia 2005; 48: 938–945.
Bergström J . Muscle electrolytes in man: determined by neutron activation analysis on needle biopsy specimens. A study on normal subjects, kidney patients and patients with chronic diarrhea. Scand J Clin Lab Invest 1962; 68 (Supplementum): 11–13.
Achten J, Gleeson M, Jeukendrup AE . Determination of the exercise intensity that elicits maximal fat oxidation. Med Sci Sports Exerc 2002; 34: 92–97.
Washburn RA, Seals DR . Comparison of peak oxygen uptake in arm cranking. Eur J Appl Physiol Occup Physiol 1983; 51: 3–6.
Smith PM, Doherty M, Price MJ . The effect of crank rate on physiological responses and exercise efficiency using a range of submaximal workloads during arm crank ergometry. Int J Sports Med 2006; 27: 199–204.
Kuznetsov AV, Veksler V, Gellerich FN, Saks V, Margreiter R, Kunz W S . Analysis of mitochondrial function in situ in permeabilized muscle fibers, tissues and cells. Nat Protoc 2008; 3: 965–976.
Brooke MH, Kaiser KK . Three ‘myosin ATPase’ systems: the nature of their pH lability and sulfhydryl dependence. J Histochem Cytochem 1970; 18: 670–672.
Qu Z, Andersen JL, Zhou S . Visualisation of capillaries in human skeletal muscle. Histochem Cell Biol 1997; 107: 169–174.
Andersen JL, Aagaard P . Myosin heavy chain IIX overshoot in human skeletal muscle. Muscle Nerve 2000; 23: 1095–1104.
Andersen JL, Schjerling P, Andersen LL, Dela F . Resistance training and insulin action in humans: effects of de-training. J Physiol 2003; 551 (Part 3): 1049–1058.
Langfort J, Ploug T, Ihlemann J, Baranczuk E, Donsmark M, Gorski J et al. Additivity of adrenaline and contractions on hormone-sensitive lipase, but not on glycogen phosphorylase, in rat muscle. Acta Physiol Scand 2003; 178: 51–60.
Helge JW, Dela F . Effect of training on muscle triacylglycerol and structural lipids: a relation to insulin sensitivity? Diabetes 2003; 52: 1881–1887.
Guerra B, Santana A, Fuentes T, gado-Guerra S, Cabrera-Socorro A, Dorado C et al. Leptin receptors in human skeletal muscle. J Appl Physiol 2007; 102: 1786–1792.
Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD et al. Measurement of protein using bicinchoninic acid. Anal Biochem 1985; 150: 76–85.
Towbin H, Staehelin T, Gordon J . Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. 1979. Biotechnology 1992; 24: 145–149.
Frayn K . Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol 1983; 55: 628–634.
Weir JB . New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 1949; 109: 1–9.
Mogensen M, Bagger M, Pedersen PK, Fernstrom M, Sahlin K . Cycling efficiency in humans is related to low UCP3 content and to type I fibres but not to mitochondrial efficiency. J Physiol 2006; 571 (Part 3): 669–681.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.
Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003; 35: 1381–1395.
Holloszy JO, Coyle EF . Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 1984; 56: 831–838.
Turcotte LP, Richter EA, Kiens B . Increased plasma FFA uptake and oxidation during prolonged exercise in trained vs untrained humans. Am J Physiol 1992; 262: E791–E799.
Horowitz JF, Klein S . Oxidation of nonplasma fatty acids during exercise is increased in women with abdominal obesity. J Appl Physiol 2000; 89: 2276–2282.
Alsted TJ, Nybo L, Schweiger M, Fledelius C, Jacobsen P, Zimmermann R et al. Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training. Am J Physiol Endocrinol Metab 2009; 296: E445–E453.
McGarry JD, Mills SE, Long CS, Foster DW . Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat. Biochem J 1983; 214: 21–28.
Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8: 1288–1295.
Saha AK, Schwarsin AJ, Roduit R, Masse F, Kaushik V, Tornheim K et al. Activation of malonyl CoA decarboxylase in rat skeletal muscle by contraction and the AMP-activated protein kinase activator AICAR. J Biol Chem 2000; 32: 24279–24283.
Jurimae J, Kums T, Jurimae T . Plasma adiponectin concentration is associated with the average accelerometer daily steps counts in healthy elderly females. Eur J Appl Physiol 2010, e-pub ahead of print 13 March 2010.
Ring-Dimitriou S, Paulweber B, von Duvillard SP, Stadlmann M, LeMura LM, Lang J et al. The effect of physical activity and physical fitness on plasma adiponectin in adults with predisposition to metabolic syndrome. Eur J Appl Physiol 2006; 98: 472–481.
Löfgren P, Andersson I, Adolfsson B, Leijonhufvud BM, Hertel K, Hoffstedt J et al. Long-term prospective and controlled studies demonstrate adipose tissue hypercellularity and relative leptin deficiency in the postobese state. Clin Endocrinol Metab 2005; 11: 6207–6213.
Muoio DM, Dohn GL, Fiedorek FT, Tapscott EB, Coleman RA . Leptin directly alters lipid partitioning in skeletal muscle. Diabetes 1997; 46: 1360–1363.
Steinberg GR, Parolin ML, Heigenhauser GJ, Dyck DJ . Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance. Am J Physiol Endocrinol Metab 2002; 283: E187–E192.
Bjorbaek C, El-Haschimi K, Frantz JD, Flier JS . The role of SOCS-3 in leptin signaling and leptin resistance. J Biol Chem 1999; 274: 30059–30065.
Steinberg GR, McAinch AJ, Chen MB, O'Brien PE, Dixon JB, Cameron-Smith D et al. The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans. J Clin Endocrinol Metab 2006; 91: 3592–3597.
Houmard JA . Do the mitochondria of obese individuals respond to exercise training? J Appl Physiol 2007; 103: 6–7.
Menshikova EV, Ritov VB, Ferrell RE, Azuma K, Goodpaster BH, Kelley DE . Characteristics of skeletal muscle mitochondrial biogenesis induced by moderate-intensity exercise and weight loss in obesity. J Appl Physiol 2007; 103: 21–27.
Ritov VB, Menshikova EV, He J, Ferrell RE, Goodpaster BH, Kelley DE . Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes 2005; 54: 8–14.
Rabol R, Svendsen PF, Skovbro M, Boushel R, Haugaard SB, Schjerling P et al. Reduced skeletal muscle mitochondrial respiration and improved glucose metabolism in nondiabetic obese women during a very low calorie dietary intervention leading to rapid weight loss. Metabolism 2009; 58: 1145–1152.
Acknowledgements
This study was supported by grants from the Novo Nordisk Foundation, The Danish Medical Research Council, The Foundation of 1870, the Christian d. 10 foundation, Programa Europa XXI—Obra Social CAI-DGA (CM 3/05 and CM 7/06) and from Gobierno de Aragon (FMI010/09).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Ara, I., Larsen, S., Stallknecht, B. et al. Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans. Int J Obes 35, 99–108 (2011). https://doi.org/10.1038/ijo.2010.123
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2010.123
Keywords
This article is cited by
-
Toward Exercise Guidelines for Optimizing Fat Oxidation During Exercise in Obesity: A Systematic Review and Meta-Regression
Sports Medicine (2023)
-
Impact of Ageing on Female Metabolic Flexibility: A Cross-Sectional Pilot Study in over-60 Active Women
Sports Medicine - Open (2022)
-
Effects of 3-month high-intensity interval training vs. moderate endurance training and 4-month follow-up on fat metabolism, cardiorespiratory function and mitochondrial respiration in obese adults
European Journal of Applied Physiology (2020)
-
Fat oxidation at rest and during exercise in male monozygotic twins
European Journal of Applied Physiology (2019)
-
Effect of regional muscle location but not adiposity on mitochondrial biogenesis-regulating proteins
European Journal of Applied Physiology (2016)