Research
Research Goal: To understand the mechanisms by which obesity influences disease by investigating the association between obesity and inflammation.
The obesity epidemic in adults and children is of concern due to associations between obesity and disease. There is strong evidence that obesity generates a low grade chronic inflammatory state that contributes to diseases such as type 2 diabetes, heart disease, asthma, and metabolic syndrome.
We are investigating the hypothesis that this obesity-induced inflammation is due to the activation of inflammatory cells in fat tissue (adipose tissue). The finding that adipose tissue contains large quantities of inflammatory cells has led to a paradigm shift in obesity research where we now recognize that obesity may be an inflammatory disease. This provides new opportunities to design strategies to evaluate patients and to treat obesity-associated diseases. Our lab investigates the biology of adipose tissue macrophages (ATMs). Macrophages are important cells that direct immune responses to infection. Surprisingly, obesity leads to the activation of ATMs in fat and the production of inflammatory proteins (cytokines) with wide ranging effects on health. Our current model of how ATMs are regulated (figure above) is being tested in the lab in patients and mouse models of obesity. ATMs in lean mice have an alternatively activated phenotype (M2; Type 2). With obesity, inflammatory monocytes are recruited to adipose tissue, differentiate into classically activated macrophages (M1; Type 1) and generate pro-inflammatory signals in fat.
Research Projects
1. Adipose tissue macrophage (ATM) polarization in health and disease
(Sponsored by NIH DK078851, DK087999, and the University of Michigan)
The functions of macrophages in adipose tissue are not fully understood. A key aspect we are trying to understand is why ATMs are found in lean states as well as in obese inflammed states.
To explain these diverse function we have focused on how ATMs can assume different activation states along the spectrum of classical (M1) and alternative (M2) activation. Research in the lab is trying to understand how these states are generated and the diversity of ATMs influences metabolism.
2. Communication between ATMs and other inflammatory cells in adipose tissue
(Sponsored by NIH DK09026, DK091976, and the University of Michigan)
The inflammatory environment in adipose tissue is very complex and involves regulation of T cells, B cells, eosinophils, and mast
cells. Currently, we lack a clear understanding of how these cells interact.
Projects in the lab are focused on understanding how ATMs interact with these cells with a current focus on ATM interactions with adipose tissue T cells.
3. Molecular regulators of ATM activation in obesity
(Sponsored by NIH DK078851, DK087999, and Pediatric Endocrine Fellow Grant)
The mechanisms by which ATMs are activated are unknown. Projects in the lab are actively investigating novel metabolic factors that are generated in adipose tissue with obesity that can activate macrophage and contribute to the inflammatory environment generated in fat.
Contact information:
Carey Lumeng MD PhD
E-mail: clumeng@umich.edu
Phone: 734-615-8708