Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor.

Metabolic flexibility of skeletal muscle, that is, the preference for fat oxidation (FOx) during fasting and for carbohydrate oxidation in response to insulin, is decreased during insulin resistance. The aim of this study was to test the hypothesis that the capacity of myotubes to oxidize fat in vitro reflects the donor's metabolic characteristics. Insulin sensitivity (IS) and metabolic flexibility of 16 healthy, young male subjects was determined by euglycemic hyperinsulinemic clamp. Muscle samples were obtained from vastus lateralis, cultured, and differentiated into myotubes. In human myotubes in vitro, we measured suppressibility (glucose suppression of FOx) and adaptability (an increase in FOx in the presence of high palmitate concentration). We termed these dynamic changes in FOx metabolic switching. In vivo, metabolic flexibility was positively correlated with IS and maximal oxygen uptake and inversely correlated with percent body fat. In vitro suppressibility was inversely correlated with IS and metabolic flexibility and positively correlated with body fat and fasting FFA levels. Adaptability was negatively associated with percent body fat and fasting insulin and positively correlated with IS and metabolic flexibility. The interindividual variability in metabolic phenotypes was preserved in human myotubes separated from their neuroendocrine environment, which supports the hypothesis that metabolic switching is an intrinsic property of skeletal muscle.

[1]  L. Jonge,et al.  Chamber for indirect calorimetry with accurate measurement and time discrimination of metabolic plateaus of over 20 min , 2003, Medical and Biological Engineering and Computing.

[2]  Imran Y. Khan,et al.  Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[3]  R. Roberts.  Impact of Maternal Diet on Reproductive Outcome: Foreword , 2004 .

[4]  J. Eckert,et al.  The Embryo and Its Future1 , 2004, Biology of reproduction.

[5]  H. Beck-Nielsen,et al.  The reduced insulin-mediated glucose oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin--evidence from cultured myotubes. , 2004, Biochimica et biophysica acta.

[6]  D. Kelley,et al.  Metabolic flexibility , 2004, The Proceedings of the Nutrition Society.

[7]  Y. Boirie,et al.  Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients , 2004, Diabetologia.

[8]  M. Prentki,et al.  AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome , 2004, Nature Reviews Drug Discovery.

[9]  H. Beck-Nielsen,et al.  Reduced lipid oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin: evidence from cultured myotubes. , 2004, Diabetes.

[10]  S. Eaton,et al.  Mitochondrial beta-oxidation. , 2004, European journal of biochemistry.

[11]  R. DeFronzo,et al.  Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. , 2004, Diabetes.

[12]  R. Unger.  Lipid overload and overflow: metabolic trauma and the metabolic syndrome , 2003, Trends in Endocrinology & Metabolism.

[13]  D. G. Newman,et al.  Muscle oxidative capacity is a better predictor of insulin sensitivity than lipid status. , 2003, The Journal of clinical endocrinology and metabolism.

[14]  A. Tremblay,et al.  Skeletal muscle enzymes as predictors of 24-h energy metabolism in reduced-obese persons. , 2003, The American journal of clinical nutrition.

[15]  S. Wakil,et al.  Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Meigs,et al.  The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging. , 2003, Diabetes.

[17]  G. Shulman,et al.  Skeletal muscle lipid metabolism with obesity. , 2003, American journal of physiology. Endocrinology and metabolism.

[18]  N. Ruderman,et al.  Insulin resistance in type 2 diabetes: association with truncal obesity, impaired fitness, and atypical malonyl coenzyme A regulation. , 2003, The Journal of clinical endocrinology and metabolism.

[19]  W. Saris,et al.  Substrate oxidation, obesity and exercise training. , 2002, Best practice & research. Clinical endocrinology & metabolism.

[20]  Jing He,et al.  Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. , 2002, Diabetes.

[21]  C. Schmitz‐Peiffer.  Protein Kinase C and Lipid‐Induced Insulin Resistance in Skeletal Muscle , 2002, Annals of the New York Academy of Sciences.

[22]  S. Kliewer,et al.  Peroxisome Proliferator-Activated Receptor-α Regulates Fatty Acid Utilization in Primary Human Skeletal Muscle Cells , 2002 .

[23]  E. Blaak,et al.  The Fate of [U-13C]Palmitate Extracted by Skeletal Muscle in Subjects With Type 2 Diabetes and Control Subjects , 2002 .

[24]  P. Havel.  Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin , 2002, Current opinion in lipidology.

[25]  B. Ljung,et al.  Correction of dysfunctional fatty acid metabolism using peroxisome proliferator activated receptor gamma agonists. , 2002, Journal of the Royal Society of Medicine.

[26]  S. Kliewer,et al.  Peroxisome proliferator-activated receptor-alpha regulates fatty acid utilization in primary human skeletal muscle cells. , 2002, Diabetes.

[27]  E. Blaak,et al.  The fate of [U-(13)C]palmitate extracted by skeletal muscle in subjects with type 2 diabetes and control subjects. , 2002, Diabetes.

[28]  Y. Terauchi,et al.  The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity , 2001, Nature Medicine.

[29]  J. Jiang,et al.  Altered GLUT1 and GLUT3 gene expression and subcellular redistribution of GLUT4: protein in muscle from patients with acanthosis nigricans and severe insulin resistance. , 2001, Metabolism: clinical and experimental.

[30]  D. Matthews,et al.  Determinants of insulin-stimulated glucose disposal in middle-aged, premenopausal women. , 2001, American journal of physiology. Endocrinology and metabolism.

[31]  T. Funahashi,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society Hypoadiponectinemia in Obesity and Type 2 Diabetes: Close Association with Insulin Resistance , 2022 .

[32]  G. Bray,et al.  Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. , 2001, Metabolism: clinical and experimental.

[33]  Simon C Watkins,et al.  Skeletal muscle lipid content and oxidative enzyme activity in relation to muscle fiber type in type 2 diabetes and obesity. , 2001, Diabetes.

[34]  G. Cooney,et al.  Triglycerides, fatty acids and insulin resistance--hyperinsulinemia. , 2001, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[35]  Hirofumi Tanaka,et al.  Age-predicted maximal heart rate revisited. , 2001, Journal of the American College of Cardiology.

[36]  G. Dohm,et al.  Lipid oxidation is reduced in obese human skeletal muscle. , 2000, American journal of physiology. Endocrinology and metabolism.

[37]  C. Bogardus,et al.  Palmitate oxidation rate and action on glycogen synthase in myoblasts from insulin-resistant subjects. , 2000, American journal of physiology. Endocrinology and metabolism.

[38]  J. Rood,et al.  Concurrent physical activity increases fat oxidation during the shift to a high-fat diet. , 2000, The American journal of clinical nutrition.

[39]  N. Ruderman,et al.  Fatty acid oxidation and the regulation of malonyl-CoA in human muscle. , 2000, Diabetes.

[40]  L. Mandarino,et al.  Fuel selection in human skeletal muscle in insulin resistance: a reexamination. , 2000, Diabetes.

[41]  J. Rood,et al.  Fat and carbohydrate balances during adaptation to a high-fat diet , 2000 .

[42]  G. Shulman,et al.  On Diabetes: Insulin Resistance Cellular Mechanisms of Insulin Resistance , 2022 .

[43]  J. Rood,et al.  Fat and carbohydrate balances during adaptation to a high-fat. , 2000, The American journal of clinical nutrition.

[44]  Rena R Wing,et al.  Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. , 1999, American journal of physiology. Endocrinology and metabolism.

[45]  N. Halaihel,et al.  Heterogeneity of pig intestinald-glucose transport systems. , 1999, American journal of physiology. Cell physiology.

[46]  A. Astrup,et al.  Lower activity of oxidative key enzymes and smaller fiber areas in skeletal muscle of postobese women. , 1998, American journal of physiology. Endocrinology and metabolism.

[47]  S. Toubro,et al.  Substrate oxidation and thyroid hormone response to the introduction of a high fat diet in formerly obese women , 1998, International Journal of Obesity.

[48]  L. Scalfi,et al.  Fasting respiratory quotient as a predictor of weight changes in non-obese women , 1998, International Journal of Obesity.

[49]  A. Astrup,et al.  Fat metabolism in formerly obese women. , 1998, American journal of physiology. Endocrinology and metabolism.

[50]  J. Simoneau,et al.  Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. , 1997, Journal of applied physiology.

[51]  K. Petersen,et al.  Mechanism of free fatty acid-induced insulin resistance in humans. , 1996, The Journal of clinical investigation.

[52]  J. Lowe,et al.  Regulation of fatty acid oxidation by acetyl-CoA generated from glucose utilization in isolated myocytes. , 1996, Journal of molecular and cellular cardiology.

[53]  S. Mudaliar,et al.  Acquired Defects of Glycogen Synthase Activity in Cultured Human Skeletal Muscle Cells: Influence of High Glucose and Insulin Levels , 1996, Diabetes.

[54]  L. Sidossis,et al.  Glucose and insulin-induced inhibition of fatty acid oxidation: the glucose-fatty acid cycle reversed. , 1996, The American journal of physiology.

[55]  L. Mandarino,et al.  Interaction of carbohydrate and fat fuels in human skeletal muscle: impact of obesity and NIDDM. , 1996, The American journal of physiology.

[56]  S. Mudaliar,et al.  Glucose transport in cultured human skeletal muscle cells. Regulation by insulin and glucose in nondiabetic and non-insulin-dependent diabetes mellitus subjects. , 1995, The Journal of clinical investigation.

[57]  R. Henry,et al.  Insulin Action and Glucose Metabolism in Nondiabetic Control and NIDDM Subjects: Comparison Using Human Skeletal Muscle Cell Cultures , 1995, Diabetes.

[58]  S. Grundy,et al.  Relationships of generalized and regional adiposity to insulin sensitivity in men. , 1995, The Journal of clinical investigation.

[59]  T. Sørensen,et al.  Dietary fat intake and weight gain in women genetically predisposed for obesity. , 1995, The American journal of clinical nutrition.

[60]  J. Simoneau,et al.  Skeletal muscle utilization of free fatty acids in women with visceral obesity. , 1995, The Journal of clinical investigation.

[61]  D. Kelley,et al.  Impaired postprandial glucose utilization in non-insulin-dependent diabetes mellitus. , 1994, Metabolism: clinical and experimental.

[62]  J. Simoneau,et al.  Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus. , 1994, The Journal of clinical investigation.

[63]  S. Toubro,et al.  Failure to increase lipid oxidation in response to increasing dietary fat content in formerly obese women. , 1994, The American journal of physiology.

[64]  Substrate utilization in man: effects of dietary fat and carbohydrate. , 1994, Metabolism: clinical and experimental.

[65]  L. Witters,et al.  Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart. , 1993, The Journal of biological chemistry.

[66]  E. Ravussin,et al.  Metabolic predictors of obesity: cross-sectional versus longitudinal data. , 1993, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[67]  L. Mandarino,et al.  Interaction between glucose and free fatty acid metabolism in human skeletal muscle. , 1993, The Journal of clinical investigation.

[68]  M. Sun,et al.  Nutrient balance and energy expenditure during ad libitum feeding of high-fat and high-carbohydrate diets in humans. , 1992, The American journal of clinical nutrition.

[69]  E. Jéquier,et al.  Interaction of lipid and carbohydrate metabolism after infusions of lipids or of lipid lowering agents: lack of a direct relationship between free fatty acid concentrations and glucose disposal. , 1992, Diabete & metabolisme.

[70]  M. Mozzoli,et al.  Effects of fat on insulin-stimulated carbohydrate metabolism in normal men. , 1991, The Journal of clinical investigation.

[71]  E. Ravussin,et al.  Muscle mitochondrial morphology, body composition, and energy expenditure in sedentary individuals. , 1991, American Journal of Physiology.

[72]  E. Ravussin,et al.  Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ. , 1990, The American journal of physiology.

[73]  W. Winder,et al.  Time course of exercise-induced decline in malonyl-CoA in different muscle types. , 1990, The American journal of physiology.

[74]  G. Pollack,et al.  Sarcomere dynamics during isotonic velocity transients in single frog muscle fibers. , 1990, The American journal of physiology.

[75]  W. Winder,et al.  Muscle malonyl-CoA decreases during exercise. , 1989, Journal of applied physiology.

[76]  R. Wolfe,et al.  Effect of elevated free fatty acids on glucose oxidation in normal humans. , 1988, Metabolism: clinical and experimental.

[77]  E. Ravussin,et al.  Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber. , 1986, The Journal of clinical investigation.

[78]  E. Ravussin,et al.  Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal. , 1984, The American journal of physiology.

[79]  H. Blau,et al.  Isolation and characterization of human muscle cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[80]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.

[81]  J. Bergström.  Percutaneous Needle Biopsy of Skeletal Muscle in Physiological and Clinical Research , 1975 .