Our overall objective is to elucidate the mechanisms that control adipocyte development and function. The ability to store energy, primarily as fat, is a fascinating property that seems to be required for the life cycle of many higher organisms. Unfortunately, abnormalities in fat accumulation produce pathological states including obesity, which is rapidly becoming one of the major causes of morbidity and mortality throughout the world. Yet, the genes that regulate adipocyte development and physiology are not fully understood. Invertebrates have proven to be powerful tools for gene discovery and for characterizing gene function. So, it would be great to have an invertebrate model for fat development. We have encouraging preliminary data that suggests that C. elegans fat might be such a model and we propose to test and exploit these initial observations. ? The specific experimental aims are: I. To study genes we identified as necessary for C. elegans fat formation. We will characterize the genes in both living worms and mammalian systems. II. To characterize the transcriptional profile of C. elegans fat with microarrays. We will compare the expression profiles of wild-type worms and worms that lack fat stores. Then, we will analyze the salient genes in worms and in mammalian systems. Ill. To identify genes required for formation of C. elegans fat via reverse and forward genetic screens. We will generate worms that lack fat by altering gene function with RNAi and with EMS mutagenesis. Then, we will characterize the responsible genes. Our long-term goal is to understand mammalian adipogenesis with the hope that understanding genes and mechanisms can lead to rational and effective treatments to relieve the suffering associated with obesity and diabetes. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK064261-04
Application #
7009915
Study Section
Metabolism Study Section (MET)
Program Officer
Haft, Carol R
Project Start
2003-03-01
Project End
2008-02-29
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
4
Fiscal Year
2006
Total Cost
$250,589
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Ugrankar, Rupali; Theodoropoulos, Pano; Akdemir, Fatih et al. (2018) Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11. Commun Biol 1:110
Jiang, Yuwei; Berry, Daniel C; Jo, Ayoung et al. (2017) A PPAR? transcriptional cascade directs adipose progenitor cell-niche interaction and niche expansion. Nat Commun 8:15926
Jiang, Yuwei; Berry, Daniel C; Graff, Jonathan M (2017) Distinct cellular and molecular mechanisms for ?3 adrenergic receptor-induced beige adipocyte formation. Elife 6:
Berry, Daniel C; Jiang, Yuwei; Arpke, Robert W et al. (2017) Cellular Aging Contributes to Failure of Cold-Induced Beige Adipocyte Formation in Old Mice and Humans. Cell Metab 25:166-181
Lapid, Kfir; Graff, Jonathan M (2017) Form(ul)ation of adipocytes by lipids. Adipocyte 6:176-186
Berry, Daniel C; Jiang, Yuwei; Graff, Jonathan M (2016) Emerging Roles of Adipose Progenitor Cells in Tissue Development, Homeostasis, Expansion and Thermogenesis. Trends Endocrinol Metab 27:574-585
Zeve, Daniel; Millay, Douglas P; Seo, Jin et al. (2016) Exercise-Induced Skeletal Muscle Adaptations Alter the Activity of Adipose Progenitor Cells. PLoS One 11:e0152129
Berry, Daniel C; Jiang, Yuwei; Graff, Jonathan M (2016) Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function. Nat Commun 7:10184
Ugrankar, Rupali; Berglund, Eric; Akdemir, Fatih et al. (2015) Drosophila glucome screening identifies Ck1alpha as a regulator of mammalian glucose metabolism. Nat Commun 6:7102
Lapid, Kfir; Lim, Ajin; Clegg, Deborah J et al. (2014) Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells. Nat Commun 5:5196

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