Our overall objective is to identify and understand the factors that control the balance of energy derived from endogenous carbohydrate, lipid, and amino acid sources during sustained, submaximal exercise. A related objective is to understand how various life situations (physical fitness, diet, gender, age) affect the balance of substrate utilization (partitioning) in humans. The theoretical basis of our approach is the 'Crossover Concept' which postulates that during rest and mild to moderate intensity exercise in the post-absorptive state, lipids provide the greatest proportion of energy for muscle and the body at large. However, as the exercise intensity increases from moderate to hard to maximal, the balance of substrate utilization in working muscle switches, or 'crosses over' from lipid to carbohydrate. Using this concept, we seek to describe the mechanisms by which exercise, exercise training, ovarian steroids, age, and dietary history affect the balance of substrate utilization. In pursuit of our overall objective, we propose to explore two specific aims. These are to: (1) describe the interactive effects of exercise intensity and endurance training on muscle and whole body fatty acid oxidation; and (2) evaluate the effects of aging and ovarian sex steroids on the balance of substrate utilization. With these data we shall be able to expand our model of substrate utilization. To assess effects of exercise intensity and to make comparisons at given relative and absolute exercise intensities before and after endurance training, for Aim 1 young men will be studied before training at power outputs (P0) that elicit 45 and 65% VO2peak; after training they will be studied at the P0 that elicited 65%V02peak before training, and at the new 65%V02 peak. To assess acute and long-term metabolic and enzymatic responses at whole-body and working muscle (leg) levels we will use the combination of tracers {[1-13C]palmitate, [1,1,2,3,3-2H2]-glycerol (D5-glycerol), and D2-glucose}, indirect calorimetry, (a-v) measurements, biopsies, and, possibly, NMR spectroscopy.
For Aim 2 studies on older men, young amenorrhic as well as older postmenopausal women we will use tracers {[1-13C]palmitate, D5-glycerol, D2- and [1-13C]glucose, as well as [1-13C]leucine}, and indirect calorimetry. On older women longitudinal designs will be employed to assess effects of training and HRT on substrate partitioning. Age-matched males will also be studied. All techniques, whether they involve exercise physiology, indirect calorimetry, tracer infusion and blood sampling, metabolite derivatization, isotopic enrichment determination by GC /MS, metabolite and hormone assays, Western blotting and dietary control, are highly developed by the investigative team. Further, we have the auxiliary personnel and facilities to conduct longitudinal training studies

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR042906-11
Application #
6782747
Study Section
Nutrition Study Section (NTN)
Program Officer
Nuckolls, Glen H
Project Start
1994-07-15
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
11
Fiscal Year
2004
Total Cost
$531,126
Indirect Cost
Name
University of California Berkeley
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Faghihnia, Nastaran; Siri-Tarino, Patty W; Krauss, Ronald M et al. (2011) Energy substrate partitioning and efficiency in individuals with atherogenic lipoprotein phenotype. Obesity (Silver Spring) 19:1360-5
Henderson, Gregory C; Krauss, Ronald M; Fattor, Jill A et al. (2010) Plasma triglyceride concentrations are rapidly reduced following individual bouts of endurance exercise in women. Eur J Appl Physiol 109:721-30
Johnson, M L; Zarins, Z; Fattor, J A et al. (2010) Twelve weeks of endurance training increases FFA mobilization and reesterification in postmenopausal women. J Appl Physiol 109:1573-81
Zarins, Zinta A; Wallis, Gareth A; Faghihnia, Nastaran et al. (2009) Effects of endurance training on cardiorespiratory fitness and substrate partitioning in postmenopausal women. Metabolism 58:1338-46
Zarins, Zinta A; Johnson, Matthew L; Faghihnia, Nastaran et al. (2009) Training improves the response in glucose flux to exercise in postmenopausal women. J Appl Physiol 107:90-7
Henderson, Gregory C; Fattor, Jill A; Horning, Michael A et al. (2008) Glucoregulation is more precise in women than in men during postexercise recovery. Am J Clin Nutr 87:1686-94
Friedlander, Anne L; Jacobs, Kevin A; Fattor, Jill A et al. (2007) Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training. Am J Physiol Endocrinol Metab 292:E107-16
Henderson, Gregory C; Fattor, Jill A; Horning, Michael A et al. (2007) Lipolysis and fatty acid metabolism in men and women during the postexercise recovery period. J Physiol 584:963-81
Wallis, Gareth A; Friedlander, Anne L; Jacobs, Kevin A et al. (2007) Substantial working muscle glycerol turnover during two-legged cycle ergometry. Am J Physiol Endocrinol Metab 293:E950-7
Henderson, Gregory C; Fattor, Jill A; Horning, Michael A et al. (2007) Retention of intravenously infused [13C]bicarbonate is transiently increased during recovery from hard exercise. J Appl Physiol 103:1604-12

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