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Research description:
The growing worldwide obesity epidemic is frequently linked to hyperlipidemia, inflammation, and insulin resistance leading to increased risk of diabetes and cardiovascular disease. The long-term goal of my laboratory is to determine mechanisms by which obesity increases risk for and pathophysiological consequences of these devastating diseases. Macrophages are part of the innate immune system that infiltrate white adipose tissue in obese rodents and humans, and produce most of the inflammatory cytokines and chemokines secreted from AT. In addition, their presence has been shown to be temporally associated with the development of insulin resistance. My current research focus is to determine mechanisms by which macrophages are attracted to adipose tissue and what happens to them once they arrive. Some of the current projects in my laboratory are:
Macrophage Cell Death: The macrophages in adipose tissue are exposed to high levels of fatty acids that are released from the adipocytes either due to uncontrolled lipolysis or adipocyte cell death. We have evidence in vitro, that exposure of macrophages to saturated fatty acids induced inflammation, ER stress and apoptosis. However, it has not been determined whether ATMs undergo apoptosis. In addition, apoptotic cells are normally phagocytosed by other macrophages in a process called “efferocytosis”. It is also now known whether efferocytosis can occur in AT in vivo. We are interested in whether efferocytosis occurs in AT and whether this can contribute to resolution of the inflammation.
Turnover of Adipose Tissue Macrophages: We have growing evidence that even in lean adipose tissue the macrophages undergo apoptotic cell death. We would like to understand how the natural turnover of macrophages contributes to the overall numbers of cells in lean and obese adipose tissue. We hypothesize that this turnover may be impaired in obesity and contribute to the accumulation of macrophages in obese adipose tissue.
Key Words: obesity, inflammation, adipose tissue, macrophage, atherosclerosis, hyperlipidemia, insulin resistance, leptin, macrophage inflammatory protein, fatty acids, nutrition
See our papers that have been highlighted in the Aliqouts Section of the Vanderbilt Reporter
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Funding:
- NIH R01 HL089466
- American Diabetes Association Bariatric Surgery Award
- NIH R21 DK095456
- Cardiovascular Medicine Predoctoral Fellowship to Andrea Hill
- ADA Postdoctoral Fellowship to Arion Kennedy
- NRSA Fellowship to Jeb Orr
- NRSA Fellowship to Dario Gutierrez
- AHA Predoctoral Fellowship to Emily Anderson
- Molecular Endocrinology Training Program Fellowship to Reid Bolus