Intramuscular triacylglycerol (TAG) content is increased with obesity and negatively associated with insulin sensitivity. The mechanisms that account for increased intramuscular TAG deposition with obesity are not clear at this time. The purpose of this proposal is to examine lipid metabolism in human skeletal muscle from obese individuals and discern the mechanism(s) responsible for intramuscular TAG accumulation. It is our primary hypothesis that human skeletal muscle from obese individuals partitions free fatty acids towards lipid storage resulting in intramuscular TAG accumulation. This hypothesis is based on our preliminary work, where in obese skeletal muscle we observed reduced free fatty acid uptake and oxidation, and a majority of uptake was partitioned to storage. These data form the basis for our working hypothesis, that TAG synthetic capacity is increased with obesity, promoting lipid storage in skeletal muscle. Our secondary hypothesis is that weight loss, which is known to decrease intramuscular lipid, will correct the defect(s) in lipid metabolism responsible for TAG accumulation.
The specific aims of this proposal are to: 1) determine intramuscular TAG content and rates of TAG synthesis and hydrolysis in muscle from nonobese and obese individuals; 2)determine activity of rate-limiting enzymes of TAG synthesis and hydrolysis in the same tissue from specific aim 1; and 3)determine the effects of weight loss on intramuscular TAG content and capacities for TAG synthesis and hydrolysis in obese individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK062605-01
Application #
6551289
Study Section
Special Emphasis Panel (ZRG1-F06 (20))
Program Officer
Hyde, James F
Project Start
2003-04-01
Project End
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$38,320
Indirect Cost
Name
East Carolina University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
Greenville
State
NC
Country
United States
Zip Code
27858
Hulver, Matthew W; Berggren, Jason R; Carper, Michael J et al. (2005) Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab 2:251-61
Berggren, Jason R; Hulver, Matthew W; Dohm, G Lynis et al. (2004) Weight loss and exercise: implications for muscle lipid metabolism and insulin action. Med Sci Sports Exerc 36:1191-5
Hulver, Matthew W; Berggren, Jason R; Cortright, Ronald N et al. (2003) Skeletal muscle lipid metabolism with obesity. Am J Physiol Endocrinol Metab 284:E741-7
Hulver, Matthew W; Houmard, Joseph A (2003) Plasma leptin and exercise: recent findings. Sports Med 33:473-82