Adipose tissue constitutes the major repository of energy stores for vertebrate organisms. In addition to its function as a site of storage and mobilization of triacylglycerols (the major lipid stored in adipose cells), it is now quite apparent that adipose cells secrete a large number of lipids and proteins, termed adipokines or adipocytokines, that can exert a wide variety of effects in an autocrine, paracrine or endocrine fashion. There is substantial evidence to support the presence of heterogeneity among adipose cells. Moreover, there are regional differences in the function of adipose depots. Adipocytes within the bone marrow might constitute a depot that is unique due to its relationship to bone. There is a strong inverse relationship between bone mass and bone marrow adipose tissue with aging and osteoporosis. The objective of this proposal is to understand the mechanisms how adipocytes, both within the bone marrow and in peripheral depots, affect bone growth and maintenance during aging.
The specific aims are 1) to test the hypothesis that adipose cells found within the bone marrow constitute a distinct depot of adipose tissue whose characteristics differ from other adipose tissue depots such that marrow adipose cells are uniquely specialized to influence bone growth and maintenance, as well as hematopoiesis;2) to test the hypothesis that the actions of hormone-sensitive lipase affect the micro-environment of the bone marrow and that removal of hormone-sensitive lipase function by gene deletion maintains high bone mass in aging mice;and 3) to identify and establish the relative importance of adipose-derived mediators responsible for influencing bone metabolism.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG028908-06
Application #
7906847
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2 (M1))
Program Officer
Williams, John
Project Start
2006-09-01
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
6
Fiscal Year
2010
Total Cost
$272,295
Indirect Cost
Name
Palo Alto Institute for Research & Edu, Inc.
Department
Type
DUNS #
624218814
City
Palo Alto
State
CA
Country
United States
Zip Code
94304
Shen, Wen-Jun; Yu, Zaixin; Patel, Shailja et al. (2011) Hormone-sensitive lipase modulates adipose metabolism through PPAR?. Biochim Biophys Acta 1811:9-16
Liu, Li-Fen; Shen, Wen-Jun; Zhang, Zhong Hua et al. (2010) Adipocytes decrease Runx2 expression in osteoblastic cells: roles of PPAR? and adiponectin. J Cell Physiol 225:837-45
Shen, Wen-Jun; Patel, Shailja; Eriksson, John E et al. (2010) Vimentin is a functional partner of hormone sensitive lipase and facilitates lipolysis. J Proteome Res 9:1786-94
Zúñiga, Luis A; Shen, Wen-Jun; Joyce-Shaikh, Barbara et al. (2010) IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J Immunol 185:6947-59
Shen, Wen-Jun; Patel, Shailja; Miyoshi, Hideaki et al. (2009) Functional interaction of hormone-sensitive lipase and perilipin in lipolysis. J Lipid Res 50:2306-13