| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1 Medicine and 2 Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; and 3 Division of Kinesiology, Department of Social and Preventive Medicine, Laval University, Ste-Foy, Quebec, Canada G1K 7P4
The current study was undertaken to
investigate fatty acid metabolism by skeletal muscle to examine
potential mechanisms that could lead to increased muscle triglyceride
in obesity. Sixteen lean and 40 obese research volunteers had leg
balance measurement of glucose and free fatty acid (FFA) uptake
(fractional extraction of [9,10
3H]oleate) and indirect
calorimetry across the leg to determine substrate oxidation during
fasting and insulin-stimulated conditions. Muscle obtained by
percutaneous biopsy had lower carnitine palmitoyl transferase (CPT)
activity and oxidative enzyme activity in obesity (P < 0.05). During fasting
conditions, obese subjects had an elevated leg respiratory quotient
(RQ, 0.83 ± 0.02 vs. 0.90 ± 0.01;
P < 0.01) and reduced fat oxidation
but similar FFA uptake across the leg. During insulin infusions, fat
oxidation by leg tissues was suppressed in lean but not obese subjects;
rates of FFA uptake were similar. Fasting values for leg RQ correlated
with insulin sensitivity (r = 
0.57, P < 0.001). Thirty-two
of the obese subjects were restudied after weight loss (WL, 14.0 ± 0.9 kg); insulin sensitivity and insulin suppression of fat
oxidation improved (P < 0.01), but
fasting leg RQ (0.90 ± 0.02 vs. 0.90 ± 0.02, pre-WL vs.
post-WL) and muscle CPT activity did not change. The findings suggest
that triglyceride accumulation in skeletal muscle in obesity derives
from reduced capacity for fat oxidation and that inflexibility in
regulating fat oxidation, more than fatty acid uptake, is related to
insulin resistance.
arteriovenous balance; indirect calorimetry; fatty acid metabolism
Deceased 27 August 1999.
This article has been cited by other articles:
|
|
 |
|
  Y. C. Long and J. R. Zierath Influence of AMP-activated protein kinase and calcineurin on metabolic networks in skeletal muscle Am J Physiol Endocrinol Metab, September 1, 2008; 295(3): E545 - E552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. J. Solomon, S. N. Sistrun, R. K. Krishnan, L. F. Del Aguila, C. M. Marchetti, S. M. O'Carroll, V. B. O'Leary, and J. P. Kirwan Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults J Appl Physiol, May 1, 2008; 104(5): 1313 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Dube, F. Amati, M. Stefanovic-Racic, F. G. S. Toledo, S. E. Sauers, and B. H. Goodpaster Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E882 - E888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Berggren, K. E. Boyle, W. H. Chapman, and J. A. Houmard Skeletal muscle lipid oxidation and obesity: influence of weight loss and exercise Am J Physiol Endocrinol Metab, April 1, 2008; 294(4): E726 - E732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Houmard Intramuscular lipid oxidation and obesity Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1111 - R1116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Jackman, A. Steig, J. A. Higgins, G. C. Johnson, B. K. Fleming-Elder, D. H. Bessesen, and P. S. MacLean Weight regain after sustained weight reduction is accompanied by suppressed oxidation of dietary fat and adipocyte hyperplasia Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2008; 294(4): R1117 - R1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Moro, S. Bajpeyi, and S. R. Smith Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E203 - E213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Devries, S. A. Lowther, A. W. Glover, M. J. Hamadeh, and M. A. Tarnopolsky IMCL area density, but not IMCL utilization, is higher in women during moderate-intensity endurance exercise, compared with men Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2007; 293(6): R2336 - R2342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Koska, E. Ortega, C. Bogardus, J. Krakoff, and J. C. Bunt The effect of insulin on net lipid oxidation predicts worsening of insulin resistance and development of type 2 diabetes mellitus Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E264 - E269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Mullen, A. C. Smith, K. A. Junkin, and D. J. Dyck Globular adiponectin resistance develops independently of impaired insulin-stimulated glucose transport in soleus muscle from high-fat-fed rats Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E83 - E90. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Smith, K. L. Mullen, K. A. Junkin, J. Nickerson, A. Chabowski, A. Bonen, and D. J. Dyck Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E172 - E181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Holloway, A. B. Thrush, G. J. F. Heigenhauser, N. N. Tandon, D. J. Dyck, A. Bonen, and L. L. Spriet Skeletal muscle mitochondrial FAT/CD36 content and palmitate oxidation are not decreased in obese women Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1782 - E1789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Savage, K. F. Petersen, and G. I. Shulman Disordered Lipid Metabolism and the Pathogenesis of Insulin Resistance Physiol Rev, April 1, 2007; 87(2): 507 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Guo, T. Pirtskhalava, T. Tchkonia, W. Xie, T. Thomou, J. Han, T. Wang, S. Wong, A. Cartwright, F. G. Hegardt, et al. Aging results in paradoxical susceptibility of fat cell progenitors to lipotoxicity Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1041 - E1051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Todd, M. J. Watt, J. Le, A. L. Hevener, and L. P. Turcotte Thiazolidinediones enhance skeletal muscle triacylglycerol synthesis while protecting against fatty acid-induced inflammation and insulin resistance Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E485 - E493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. W. Booth and S. J. Lees Fundamental questions about genes, inactivity, and chronic diseases Physiol Genomics, January 17, 2007; 28(2): 146 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Turpin, G. I. Lancaster, I. Darby, M. A. Febbraio, and M. J. Watt Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1341 - E1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Perseghin, R. Bonfanti, S. Magni, G. Lattuada, F. De Cobelli, T. Canu, A. Esposito, P. Scifo, G. Ntali, F. Costantino, et al. Insulin resistance and whole body energy homeostasis in obese adolescents with fatty liver disease Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E697 - E703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R Wolfe The underappreciated role of muscle in health and disease. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 475 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Smith and G. E. O. Muscat Orphan nuclear receptors: therapeutic opportunities in skeletal muscle Am J Physiol Cell Physiol, August 1, 2006; 291(2): C203 - C217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schenk and J. F. Horowitz Coimmunoprecipitation of FAT/CD36 and CPT I in skeletal muscle increases proportionally with fat oxidation after endurance exercise training Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E254 - E260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Bruce, A. B. Thrush, V. A. Mertz, V. Bezaire, A. Chabowski, G. J. F. Heigenhauser, and D. J. Dyck Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content Am J Physiol Endocrinol Metab, July 1, 2006; 291(1): E99 - E107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kiens Skeletal Muscle Lipid Metabolism in Exercise and Insulin Resistance Physiol Rev, January 1, 2006; 86(1): 205 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-S. Cha, T. P. Ciaraldi, K.-S. Park, L. Carter, S. R. Mudaliar, and R. R. Henry Impaired fatty acid metabolism in type 2 diabetic skeletal muscle cells is reversed by PPAR{gamma} agonists Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E151 - E159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. V. Menshikova, V. B. Ritov, F. G. S. Toledo, R. E. Ferrell, B. H. Goodpaster, and D. E. Kelley Effects of weight loss and physical activity on skeletal muscle mitochondrial function in obesity Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E818 - E825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schenk, J. N. Cook, A. E. Kaufman, and J. F. Horowitz Postexercise insulin sensitivity is not impaired after an overnight lipid infusion Am J Physiol Endocrinol Metab, March 1, 2005; 288(3): E519 - E525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Venables, J. Achten, and A. E. Jeukendrup Determinants of fat oxidation during exercise in healthy men and women: a cross-sectional study J Appl Physiol, January 1, 2005; 98(1): 160 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Barazzoni, A. Bosutti, M. Stebel, M. R. Cattin, E. Roder, L. Visintin, L. Cattin, G. Biolo, M. Zanetti, and G. Guarnieri Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E228 - E235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Thyfault, R. M. Kraus, R. C. Hickner, A. W. Howell, R. R. Wolfe, and G. L. Dohm Impaired plasma fatty acid oxidation in extremely obese women Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1076 - E1081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pruchnic, A. Katsiaras, J. He, D. E. Kelley, C. Winters, and B. H. Goodpaster Exercise training increases intramyocellular lipid and oxidative capacity in older adults Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E857 - E862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. He and D. E. Kelley Muscle glycogen content in type 2 diabetes mellitus Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E1002 - E1007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Bruce and D. J. Dyck Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-{alpha} Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E616 - E621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-H. Han, L. A. Nolte, J.-S. Ju, T. Coleman, J. O. Holloszy, and C. F. Semenkovich UCP-mediated energy depletion in skeletal muscle increases glucose transport despite lipid accumulation and mitochondrial dysfunction Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E347 - E353. [Abstract] [Full Text]
|
|
|
|
|
|
J. Zhang, D. I. W. Phillips, C. Wang, and C. D. Byrne Human skeletal muscle PPAR{alpha} expression correlates with fat metabolism gene expression but not BMI or insulin sensitivity Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E168 - E175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Steinberg, A. C. Smith, S. Wormald, P. Malenfant, C. Collier, and D. J. Dyck Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E57 - E63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Z. Tucker and L. P. Turcotte Aging is associated with elevated muscle triglyceride content and increased insulin-stimulated fatty acid uptake Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E827 - E835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Ukkola, D. R. Joanisse, A. Tremblay, and C. Bouchard Na+-K+-ATPase alpha 2-gene and skeletal muscle characteristics in response to long-term overfeeding J Appl Physiol, May 1, 2003; 94(5): 1870 - 1874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Gray, C. J. Tanner, W. J. Pories, K. G. MacDonald, and J. A. Houmard Effect of weight loss on muscle lipid content in morbidly obese subjects Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E726 - E732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Hulver, J. R. Berggren, R. N. Cortright, R. W. Dudek, R. P. Thompson, W. J. Pories, K. G. MacDonald, G. W. Cline, G. I. Shulman, G. L. Dohm, et al. Skeletal muscle lipid metabolism with obesity Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E741 - E747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Mittendorfer, B. W. Patterson, and S. Klein Effect of weight loss on VLDL-triglyceride and apoB-100 kinetics in women with abdominal obesity Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E549 - E556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Clerk, M. E. Smith, S. Rattigan, and M. G. Clark Nonnutritive flow impairs uptake of fatty acid by white muscles of the perfused rat hindlimb Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E611 - E617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Perseghin, P. Scifo, M. Danna, A. Battezzati, S. Benedini, E. Meneghini, A. Del Maschio, and L. Luzi Normal insulin sensitivity and IMCL content in overweight humans are associated with higher fasting lipid oxidation Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E556 - E564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Steinberg, M. L. Parolin, G. J. F. Heigenhauser, and D. J. Dyck Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E187 - E192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Tanner, H. A. Barakat, G. L. Dohm, W. J. Pories, K. G. MacDonald, P. R. G. Cunningham, M. S. Swanson, and J. A. Houmard Muscle fiber type is associated with obesity and weight loss Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1191 - E1196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. McGarry Banting Lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes Diabetes, January 1, 2002; 51(1): 7 - 18. [Full Text] [PDF]
|
|
|
|
|
|
F. Diraison, E. Dusserre, H. Vidal, M. Sothier, and M. Beylot Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity Am J Physiol Endocrinol Metab, January 1, 2002; 282(1): E46 - E51. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mensink, E. E. Blaak, M. A. van Baak, A. J.M. Wagenmakers, and W. H.M. Saris Plasma Free Fatty Acid Uptake and Oxidation Are Already Diminished in Subjects at High Risk for Developing Type 2 Diabetes Diabetes, November 1, 2001; 50(11): 2548 - 2554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Hevener, D. Reichart, A. Janez, and J. Olefsky Thiazolidinedione Treatment Prevents Free Fatty Acid-Induced Insulin Resistance in Male Wistar Rats Diabetes, October 1, 2001; 50(10): 2316 - 2322. [Abstract] [Full Text]
|
|
|
|
|
|
A. Virkamaki, E. Korsheninnikova, A. Seppala-Lindroos, S. Vehkavaara, T. Goto, J. Halavaara, A.-M. Hakkinen, and H. Yki-Jarvinen Intramyocellular Lipid Is Associated With Resistance to In Vivo Insulin Actions on Glucose Uptake, Antilipolysis, and Early Insulin Signaling Pathways in Human Skeletal Muscle Diabetes, October 1, 2001; 50(10): 2337 - 2343. [Abstract] [Full Text]
|
|
|
|
|
|
D. J. Dyck, G. Steinberg, and A. Bonen Insulin increases FA uptake and esterification but reduces lipid utilization in isolated contracting muscle Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E600 - E607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Hickner, J. Privette, K. McIver, and H. Barakat Fatty acid oxidation in African-American and Caucasian women during physical activity J Appl Physiol, June 1, 2001; 90(6): 2319 - 2324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Kelley and B. H. Goodpaster Skeletal Muscle Triglyceride: An aspect of regional adiposity and insulin resistance Diabetes Care, May 1, 2001; 24(5): 933 - 941. [Abstract] [Full Text]
|
|
|
|
|
|
J. He, S. Watkins, and D. E. Kelley Skeletal Muscle Lipid Content and Oxidative Enzyme Activity in Relation to Muscle Fiber Type in Type 2 Diabetes and Obesity Diabetes, April 1, 2001; 50(4): 817 - 823. [Abstract] [Full Text]
|
|
|
|
|
|
P. Malenfant, A. Tremblay, E. Doucet, P. Imbeault, J.-A. Simoneau, and D. R. Joanisse Elevated intramyocellular lipid concentration in obese subjects is not reduced after diet and exercise training Am J Physiol Endocrinol Metab, April 1, 2001; 280(4): E632 - E639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Guesbeck, M. S. Hickey, K. G. MacDonald, W. J. Pories, I. Harper, E. Ravussin, G. L. Dohm, and J. A. Houmard Substrate utilization during exercise in formerly morbidly obese women J Appl Physiol, March 1, 2001; 90(3): 1007 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Kim, R. C. Hickner, R. L. Cortright, G. L. Dohm, and J. A. Houmard Lipid oxidation is reduced in obese human skeletal muscle Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1039 - E1044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Goodpaster, D. E. Kelley, F. L. Thaete, J. He, and R. Ross Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content J Appl Physiol, July 1, 2000; 89(1): 104 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Imbeault, A. Tremblay, J.-A. Simoneau, and D. R. Joanisse Weight loss-induced rise in plasma pollutant is associated with reduced skeletal muscle oxidative capacity Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E574 - E579. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS |
