Depot-specific gene expression programs of adipocytes : physiological and developmental implications
Abstract/Contents
- Abstract
- Adipose tissue is found in diverse depots throughout the human body. The diversity of physiological specialization of these fat depots is reflected in the diverse depot-specific alterations seen in lipodystrophies and links between specific patterns of fat distribution and susceptibility to diseases, including Type II Diabetes and coronary artery disease. Previous studies, although focused on only 2 major fat depots (omental and abdominal subcutaneous), have identified numerous differences in metabolic, endocrine and developmental programs. We carried out a more extensive and higher resolution investigation of the anatomic specialization of white adipose tissue, based on 59 samples collected from 7 anatomically diverse fat depots, from 56 individuals. Using DNA microarrays we measured relative abundance of ~25,000 distinct mRNAs in each adipose tissue sample and in adipocytes and stromal-vascular cells isolated from each sample, and compared their gene expression patterns with ~120 samples representing diverse non-adipose tissues. Adipocytes from different regions of the body displayed distinct gene expression profiles. Characteristic patterns of expression of HOX genes distinguished adipocyte samples by site of origin; these patterns were recapitulated when adipocyte precursors from each site were cultured and differentiated ex vivo, suggesting that these genes may have a role in programming and/or maintaining depot-specific differentiation of adipocytes. Expression in adipocytes of 300 genes with major roles in energy metabolism showed both depot-dependent and inter-individual variation. Some of the patterns suggested important differences among anatomic depots in metabolic roles. For example, a set of genes involved in lipid uptake and storage and hormone-regulated lipolysis were generally most highly expressed in breast, pericolonic and omental adipocytes whereas genes involved in glycogen metabolism and de novo fatty acid synthesis were generally most highly expressed in breast and abdominal subcutaneous adipocytes, suggesting that these depots play a role as glucose buffers. Dozens of genes known or predicted to encode secreted molecular signals were highly expressed in adipocytes compared to either adipose stromal-vascular cells or other organs; many of these were differentially expressed among adipocyte depots. Some of these genes appear to be good candidates for encoding novel adipokines. In summary, we found extensive variation among adipose depots, as well as inter-individual variation, in global gene expression. Differences in genes linked to development, metabolism and cell-cell communication suggest new hypotheses relevant to depot-specific and general aspects of adipocyte biology.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Clemons, Heather Jean |
|---|---|
| Associated with | Stanford University, Department of Biochemistry. |
| Primary advisor | Brown, Patrick O'Reilly, 1954- |
| Thesis advisor | Brown, Patrick O'Reilly, 1954- |
| Thesis advisor | Chu, Gilbert |
| Thesis advisor | Kingsley, David M. (David Mark) |
| Thesis advisor | Krasnow, Mark, 1956- |
| Advisor | Chu, Gilbert |
| Advisor | Kingsley, David M. (David Mark) |
| Advisor | Krasnow, Mark, 1956- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Heather Jean Clemons. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Ph.D. Stanford University 2010 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Heather Jean Clemons
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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