Carey Lumeng, M.D., Ph.D.
Ongoing projects in the lab are focused on understanding the function of leukocytes in adipose tissue and the mechanisms by which they area actived obesity. Animal models of obesity are utilized to explore how the manipulation of inflammatory cell function impacts nutrient metabolism (e.g. insulin resistance). We employ a wide range of in vitro, in vivo, and advanced imaging modalities to characterize adipose tissue inflammation.
1. Adipose tissue macrophages (ATMs) as antigen presenting cells - Studies are underway to evaluate communication between macrophage and T cells in fat and how these pathways regulate nutrient metabolism.
2. Mechanisms of M1 activation of ATMs - With obesity, ATMs take on an M1 pro-inflammatory profile. The mechanisms of this relates to chemokine mediated monocyte trafficking to fat and knockout mice are utilized to identify the critical pathways.
3. Interaction between nutrients and macrophage inflammation - The mechanisms why which nutrients influence inflammation are being explored. This includes the effects of fatty acids, glucose, adipokines, lipids, and stress hormones on the action of macrophage, dendritic cells, and lymphocytes that can explain the inflammatory activation with obesity.
4. Intravital imaging of adipose tissue inflammation - In vivo imaging of adipose tissue leukocytes is being performed in the lab to understand the interactions between macrophages, lymphocytes, adipocytes and vasculature in adipose tissue. This is revealing novel dynamic interactions between these cells in lean and obese settings. These studies employ multiphoton confocal microscopy and live cell imaging techniques in genetically engineered mice.
Inflammatory links between obesity and metabolic disease. Lumeng CN, Saltiel AR. J Clin Invest. 2011 Jun 1;121(6):2111-7.
Deiuliis, J., Shah, Z., Shah, N., Needleman, B., Mikami, D., Narula, V., Perry, K., Hazey, J., Kampfrath, T., Kollengode, M., Sun, Q., Satoskar, A.R., Lumeng, C., Moffatt-Bruce, S., Rajagopalan, S. Visceral adipose inflammation in obesity is associated with critical alterations in tregulatory cell numbers. PLoS One. 6(1):e16376, 2011.
Westcott, D., DelProposto, J., Geletka, L., Wang, T., Kanakadurga, S., Saltiel, A., Lumeng, C.N. MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med, 206(13):3143-3156, 2009.
Lumeng CN, Maillard I, Saltiel AR. T-ing up inflammation in fat. Nat Med 2009 Aug;15(8):846-847
Lumeng, C.N., DelProposto, J.B., Westcott, D. and Saltiel, A.R. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes, 57(12):3239-46, 2008.
Lumeng, C.N., Bodzin, J.L., and Saltiel, A.R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. Journal of Clinical Investigation, 117(1):175-184, 2007.
Lumeng, C.N., DeYoung, S.M., and Saltiel, A.R. Macrophages induce insulin resistance in adipocytes by altering expression of signaling and glucose transport proteins. American Journal of Physiology: Endocrinology and Metabolism.292(1):E166-174. 2007.
Lumeng, C.N., DeYoung, S.M., Bodzin, J.L. and Saltiel, A.R. Increased inflammatory properties of adipose tissue macrophages recruited during diet induced obesity. Diabetes, 6(1):16-23, 2007.