| City: |
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San Diego |
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State:
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CA |
| Zip Code: |
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92103 |
| Conditions: |
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Morbid Obesity - Hyperglycemia - Diabetes Mellitus |
| Purpose: |
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A research study to find out more about a specific white blood cell called a dendritic cell.
These cells are found in a layer of fat in the body called the omentum. The omentum is a
layer of fat that covers the bowels (intestines) and protects them.
The purpose of this study is to allow us to compare dendritic cells in normal weight
individuals to the dendritic cells of people who are extremely overweight. These cells
will be collected from the omentum, the layer of fat that covers and protects the bowels
(intestines), from the mesentery, which is another layer of fat that surrounds the
intestines directly, and from the subcutaneous tissue, which is the layer of fat just under
the skin.
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| Study summary: |
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Obesity continues to be a major source of morbidity and mortality in the United States. The
association between obesity and type II diabetes is well known. Several studies suggest that
fat may generate a low grade inflammatory response that may be responsible for the metabolic
changes in obese patients. More specifically, a certain type of white blood cell that causes
inflammation called a dendritic cell has been found in high concentrations in omental fat.
This cell has not been extensively studied in human patients with morbid obesity, though it
may play a central role in the development of insulin resistance. Aside from weight loss,
the surgical treatment of obesity also results in a decrease in the markers of inflammation.
Many of the comorbidities of morbid obesity improve or are cured. Laparoscopic adjustable
gastric banding is safer than other gastric bypass procedures and results in similar amounts
of weight loss after 2 years postoperatively.
Much of the work regarding dendritic cells in human subjects has been in patients with
Crohn's disease. Both the cytokine profile and characteristics of the dendritic cells have
been extensively studied in Crohn's patients, but not in obese individuals. In addition to
this, these cells have not been re-evaluated after a period of weight loss.
A more detailed analysis of the inflammation of obesity and its subsequent resolution with
weight loss will contribute to the growing body of information on this subject. Further work
will lend insight into the pathogenesis of the comorbidities of obesity and may contribute
to uncovering potential treatments for these illnesses. Dendritic cells have been
extensively studied in animal models. We now know specific cell surface markers and
signaling pathways for these cells, their responses to stimulating factors, and their
ability to secrete anti-inflammatory cytokines such as IL-10. We hope to translate these
findings to humans.
It is now recognized that chronic low-grade inflammation is the critical element leading to
insulin resistance in insulin target cells. The evidence for this is substantial, including
consistent measurements of elevated inflammatory markers in plasma from insulin
resistance/diabetic humans and rodents. This concept was further established by the recent
discovery that obese adipose tissue contains large numbers of resident macrophages. In
fact, in the lean state, about 10% of all the cell types within adipose tissue consist of
macrophages, and this number can go as high as 50% in obesity. Furthermore, FACS sorting of
adipose tissue macrophages based on surface markers, has indicated that it is a
subpopulation of macrophages which accounts for this remarkable increase. This
subpopulation involves macrophages which are positive for F4/80, CD11B and CD11C and are,
therefore, dendritic-like in their phenotype. There are also reports in the literature which
suggests that visceral adipose tissue may be particularly "inflamed" compared to
subcutaneous adipose tissue and that increased macrophage infiltration and inflammatory
markers are expressed in visceral fat. More recent evidence, in which the macrophage
inflammatory pathway is specifically disabled, in knock-out mice, conclusively demonstrates
that the macrophage can be the initiating or orchestrating cell type responsible for the
inflammatory response which ultimately leads to systemic insulin resistance.
These concepts will be assessed in using the subcutaneous and visceral fat samples obtained
under this protocol. The adipose tissue samples will be collagenase digested to release all
of the adipocytes and non-adipocyte cell types within the tissue. Using differential
centrifugation and filtration, the stromal vascular fraction (SVF) will be separated from
the adipocytes. The SVF contains the macrophages, and these cells will undergo FACS
analysis based on the expression of F4/80, CD11B and CD11C to determine the absolute number
of macrophages within a given adipose tissue sample, and the proportion of classical
macrophages versus dendritic cell-like macrophages. The cells will then be sorted, and
inflammatory marker expression will be measured in the classical macrophages (F4/80
positive, CD11B positive, but CD11C negative) versus the dendritic-like cells (F480
positive, CD11B positive, and CD11C positive). This analysis will involve direct
measurement of cytokine expression by these cells (TNF, IL-1, and IL-6) as well as PCR-based
measurements of mRNA expression of inflammatory pathway components. These measurements will
be performed on the subcutaneous and visceral adipose tissue obtained at the time of the
initial surgery, as well as on the subcutaneous adipose tissue samples at follow up after
weight reduction. |
| Criteria: |
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Inclusion Criteria:
- For gastric banding subjects to qualify for study inclusion, subjects have to have a
BMI ranging from 33-40. Currently a BMI of 33 is our lower level of acceptable for
bypass. Subjects with a BMI>40 will be excluded because their fat cells are very
large and therefore fragile and unsuitable for research use.
Control Group:
- All adult subjects 18 years or greater being seen in the minimally invasive surgery
clinic for elective laparoscopic surgery will also be screened.
- These will be subjects who are non-obese (BMI<30) and undergoing laparoscopic surgery
for a different indication such as hernia repair or cholecystectomy. These will be
patients who are undergoing elective procedures to minimize the impact an acute
inflamed abdomen may have on the fat cells.
Exclusion Criteria:
- Women who are pregnant or planning to become pregnant will be excluded from this
study. Gastric banding cannot not be performed on pregnant women. |
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| Study is available at: |
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UCSD Healthcare
San Diego, CA 92103
United States
Primary Contact:
Julie A Bosia, BSN
Email: jbosia@ucsd.edu
Phone: 619-471-0774 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 22, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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