The overall goal of these studies is to better understand factor that cause overeating-driven metabolic disease. We are using skeletal muscle, primary site of nutrient deposal, to address the role of protein that coat the myocellular fat depot (the perilipins) play in regulating the fat they enclose and how this regulation fat influences susceptibility to metabolic disease. We hypothesis: perilipin 5 forms the myocellular fat storage organelle;only fat in this organelle is under appropriate myocellular regulation;and perilipin 5 levels determine the fat storage capacity of organelle and the overflow this organelle cause metabolically disruptive lipid to leak in the cytosol. Thus, we predict that increasing perilipin 5 levels will increase resistant to metabolic challenges. We will determine: the effects of perilipins on cellular fat packaging and release;what lipid intermediates and key metabolic proteins perilipin 5 recruits fat droplets to regulate fat flux;and affect of muscle-specific overexpression and ablation of perilipin 5 on lipid metabolism, insulin sensitivity and levels of metabolically disruptive lipid.

Public Health Relevance

We burn large amounts of food energy in our skeletal muscle, but eating more food than we burn leads to obesity. How fat is transported inside muscle cells and what regulates how fast fat is burned in muscle is not well understood. We propose to study the proteins in muscle cells that coat fat, and that transport fat into storage or direct fat to be burned as fuel.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK088206-02
Application #
8217238
Study Section
Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
Program Officer
Pawlyk, Aaron
Project Start
2011-02-01
Project End
2016-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
2
Fiscal Year
2012
Total Cost
$330,600
Indirect Cost
$113,100
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Skinner, James R; Harris, Lydia-Ann L S; Shew, Trevor M et al. (2013) Perilipin 1 moves between the fat droplet and the endoplasmic reticulum. Adipocyte 2:80-6
Harris, Lydia-Ann L S; Skinner, James R; Wolins, Nathan E (2013) Imaging of neutral lipids and neutral lipid associated proteins. Methods Cell Biol 116:213-26
Brasaemle, Dawn L; Wolins, Nathan E (2012) Packaging of fat: an evolving model of lipid droplet assembly and expansion. J Biol Chem 287:2273-9
Harris, Lydia-Ann L S; Shew, Trevor M; Skinner, James R et al. (2012) A single centrifugation method for isolating fat droplets from cells and tissues. J Lipid Res 53:1021-5