Significant evidence suggests that skeletal muscle lipoprotein lipase (LPL) activity is a major determinant of triglyceride and lipoprotein metabolism. It is well documented that exercise training increases skeletal muscle LPL activity, decreases plasma triglycerides, increases HDL-cholesterol, and reduces the incidence of coronary artery disease. The long-term objective of the proposed investigations is to determine, at the level of the LPL gene, the mechanisms(s) by which exercise training increases skeletal muscle LPL mRNA expression.
The first aim of the proposed studies is to systematically establish the time course, exercise duration, and muscles that LPL mRNA is increased in run-trained rats. It is hypothesized that during exercise training, LPL mRNA increases after each exercise session to peak several hours after exercise and then gradually falls to untrained sedentary levels within 24-48 hours of rest. It is also hypothesized that 10 min. of intense running or electrical stimulation of the motor nerve is sufficient to increase skeletal muscle LPL mRNA. These studies will measure the transcription rate of LPL in skeletal muscles of run trained and sedentary control animals. Deletion and mutation experiments on the LPL promoter will determine essential and necessary gene sequences for exercise induced LPL promoter regions. Alternative experiments are planned to test for the involvement of the 3'-untranslated region of LPL in causing the exercise-induced increase in LPL expression. These findings will elucidate the molecular mechanism of increased LPL mRNA levels during exercise training, and thus will be essential for identifying the biochemical signaling pathway(s) involved in exercise increased LPL expression and improved blood lipids.
These specific aims are at the interphase of linking molecular mechanisms regulating LPL expression to the prevention of morbidity and mortality caused by coronary artery disease, the leading cause of death in the United States.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL057367-01A1
Application #
2405464
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1997-08-01
Project End
2001-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Biology
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Hamilton, Marc T; Hamilton, Deborah G; Zderic, Theodore W (2014) Sedentary behavior as a mediator of type 2 diabetes. Med Sport Sci 60:11-26
Bey, Lionel; Akunuri, Nagabhavani; Zhao, Po et al. (2003) Patterns of global gene expression in rat skeletal muscle during unloading and low-intensity ambulatory activity. Physiol Genomics 13:157-67
Bey, Lionel; Hamilton, Marc T (2003) Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity. J Physiol 551:673-82
Bey, Lionel; Maigret, Pascal; Laouenan, Herve et al. (2002) Induction of lipoprotein lipase gene expression in 3T3-L1 preadipocytes by atorvastatin, a cholesterol- and triglyceride-lowering drug. Pharmacology 66:51-6
Bey, L; Areiqat, E; Sano, A et al. (2001) Reduced lipoprotein lipase activity in postural skeletal muscle during aging. J Appl Physiol 91:687-92
Hamilton, M T; Areiqat, E; Hamilton, D G et al. (2001) Plasma triglyceride metabolism in humans and rats during aging and physical inactivity. Int J Sport Nutr Exerc Metab 11 Suppl:S97-104
Campbell, W G; Gordon, S E; Carlson, C J et al. (2001) Differential global gene expression in red and white skeletal muscle. Am J Physiol Cell Physiol 280:C763-8
Booth, F W; Gordon, S E; Carlson, C J et al. (2000) Waging war on modern chronic diseases: primary prevention through exercise biology. J Appl Physiol 88:774-87
Fluck, M; Waxham, M N; Hamilton, M T et al. (2000) Skeletal muscle Ca(2+)-independent kinase activity increases during either hypertrophy or running. J Appl Physiol 88:352-8
Hamilton, M T; Booth, F W (2000) Skeletal muscle adaptation to exercise: a century of progress. J Appl Physiol 88:327-31

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