Mechanisms How Adipocytes Affect Bone in Aging Mice

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DESCRIPTION (provided by applicant): 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.