Two thirds of Americans are overweight or obese. Excess body fat, particularly in the abdomen, has been linked to cardiovascular disease, type 2 diabetes, certain forms of cancer and other medical conditions. Strategies to prevent weight gain or its harmul effects on health have had limited success. This project will investigate how certain types of fat-toring cells (adipocytes) are produced in abdominal fat. The results may identify new targets for therapie to prevent weight gain and fat-related chronic disease. Over the last 7 years we have identified a population of adipocytes that are produced from stem cells in the bone marrow. These stem cells leae the marrow and travel to fat tissue where they become new adipocytes. These bone marrow-derived adipocytes accumulate preferentially in abdominal fat in female animals, and exhibit potentially hamful characteristics. This project is designed to determine why these cells are produced in abdominal fa, and if their production is more rapid than other types of fat-storing cells.
The first aim will tes whether the inflammatory protein, monocyte inhibitory protein-1a (MIP-1a), promotes the recruitment of stem cells from the bone marrow to fat and the subsequent generation of bone marrow-derived adipocyte in abdominal fat. This will be accomplished by following labeled marrow progenitors to fat tissue in mce in which MIP-1a has been genetically erased.
Aim 2 will test whether the ovarian hormones, estrogen an progesterone, are also involved in bone marrowadipocyte production and account for the preferential accumulation of these fat cells in female subjects. Finally, Aim 3 will use a novel labeling technoogy to measure the rate at which bone marrow-derived adipocytes and other fat-storing cells are produced i fat in different body locations. Completion of these studies will provide a comprehensive picture o the factors and processes that control bone marrow-derived adipocyte production. The results are likelyto highlight new targets for controlling the generation of these fat cells and thereby mitigate their armful effects on health. The results may also ex- plain why fat is stored differently between men and womn, and why fat storage in women changes after menopause. We predict that these experiments will furthe underscore the importance of stem cells and progenitor cells in the development of fat in differentbody locations and its differential impact on health.

Public Health Relevance

Obesity is a major medical problem for which there are few effective therapies. This project will investigate why certain types of fat cells with potentially harmful characteristics are produced in specific body locations and in greater numbers in female than male subjects. Successful completion of these studies will identify new targets for controlling the prodction of harmful fat-storing cells and prevent fat-related chronic disease.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado Denver
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Gavin, Kathleen M; Kohrt, Wendy M; Klemm, Dwight J et al. (2018) Modulation of Energy Expenditure by Estrogens and Exercise in Women. Exerc Sport Sci Rev 46:232-239
Gavin, Kathleen M; Sullivan, Timothy M; Kohrt, Wendy M et al. (2018) Ovarian Hormones Regulate the Production of Adipocytes From Bone Marrow-Derived Cells. Front Endocrinol (Lausanne) 9:276
Reusch, Jane E B; Kumar, T Rajendra; Regensteiner, Judith G et al. (2018) Identifying the Critical Gaps in Research on Sex Differences in Metabolism Across the Life Span. Endocrinology 159:9-19
Gavin, Kathleen M; Majka, Susan M; Kohrt, Wendy M et al. (2017) Hematopoietic-to-mesenchymal transition of adipose tissue macrophages is regulated by integrin ?1 and fabricated fibrin matrices. Adipocyte 6:234-249
Ye, Haobin; Adane, Biniam; Khan, Nabilah et al. (2016) Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche. Cell Stem Cell 19:23-37
Gavin, Kathleen M; Gutman, Jonathan A; Kohrt, Wendy M et al. (2016) De novo generation of adipocytes from circulating progenitor cells in mouse and human adipose tissue. FASEB J 30:1096-108
Majka, Susan M; Miller, Heidi L; Helm, Karen M et al. (2014) Analysis and isolation of adipocytes by flow cytometry. Methods Enzymol 537:281-96
West, James D; Austin, Eric D; Gaskill, Christa et al. (2014) Identification of a common Wnt-associated genetic signature across multiple cell types in pulmonary arterial hypertension. Am J Physiol Cell Physiol 307:C415-30
McCurdy, Carrie E; Klemm, Dwight J (2013) Adipose tissue insulin sensitivity and macrophage recruitment: Does PI3K pick the pathway? Adipocyte 2:135-42
Majka, Susan M; Miller, Heidi L; Sullivan, Timothy et al. (2012) Adipose lineage specification of bone marrow-derived myeloid cells. Adipocyte 1:215-229

Showing the most recent 10 out of 15 publications