Lipoprotein lipase (LPL) is an important enzyme in lipid metabolism. Abnormalities in LPL activity are associated with numerous diseases including coronary heart disease, diabetes mellitus, and obesity. Defects in LPL activity frequently result in hypertriglyceridemia which is observed commonly in the general population. Hypertriglyceridemia, especially in women, is often associated with human atherosclerosis although its role in this disease is uncertain. The long-term objectives of this application will be to study the role LPL plays in hypertriglyceridemia and coronary heart disease in men and women, to define the mechanisms responsible for defects in LPL activity, and to determine how diet affects LPL in men and women. This application therefore consists of clinical studies involving women as well as men.
The specific aims of this application are: -To define the structural abnormalities of the LPL gene responsible for the clinical abnormalities of individuals with familial LPL deficiency. Subjects with Type 1 hyperlipoproteinemia and selected relatives will be studied with the use of Polymerase Chain Reaction (PCR) techniques and DNA sequencing. -To determine the frequency of common LPL gene mutations in a cohort of subjects who have recently suffered a myocardial infarction. Genomic DNA from such patients as well as from members of a control group will be studied by a combination of PCR and allele-specific oligonucleotide hybridization techniques. -To study the tissue-specific regulation of human LPL by diets differing in the composition of saturated, n-6 polyunsaturated, and n-3 polyunsaturated fatty acids. LPL enzyme activity, LPL protein mass determined by ELISA, and LPL mRNA measured by RNase protection will be studied in human adipose tissue and skeletal muscle.
| Ren, J M; Semenkovich, C F; Gulve, E A et al. (1994) Exercise induces rapid increases in GLUT4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscle. J Biol Chem 269:14396-401 |
| Ostlund Jr, R E; Yang, J W; Heath-Monnig, E et al. (1994) Increased low density lipoprotein receptor expression mediated through the insulin-like growth factor-I receptor in cultured fibroblasts. Mol Endocrinol 8:904-9 |
| Semenkovich, C F; Coleman, T; Goforth, R (1993) Physiologic concentrations of glucose regulate fatty acid synthase activity in HepG2 cells by mediating fatty acid synthase mRNA stability. J Biol Chem 268:6961-70 |
| Ren, J M; Semenkovich, C F; Holloszy, J O (1993) Adaptation of muscle to creatine depletion: effect on GLUT-4 glucose transporter expression. Am J Physiol 264:C146-50 |
