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chait-20111

Alan Chait, M.D.

Division of Metabolism, Endocrinology and Nutrition

Division Head
Edwin L. Bierman Professor of Medicine


Focus

Dr. Chait’s research focuses on lipoprotein-proteoglycan interactions in atherogenesis; the role of diabetes in the pathogenesis of macrovascular disease; and the links amongst obesity, inflammation, insulin resistance and atherosclerosis.


Summary


Dr. Chait received his MBChB (MD equivalent) and his MD (PhD equivalent) from the University of Cape Town, South Africa. After completing an internship at Groote Schuur Hospital in Cape Town, he finished his residency and a research fellowship at the Hammersmith Hospital, Royal Postgraduate Medical School, in London, UK. He next became a lecturer in Endocrinology at the London Hospital. He came to the UW as a senior research fellow in Metabolism and Endocrinology in 1975, and was appointed to the faculty in 1977. In 1985 he was appointed Professor of Medicine, and became Head of the Division on Metabolism, Endocrinology and Nutrition in 1996. In addition to clinical teaching and patient care responsibilities at the University of Washington Medical Center, since 1977 Dr. Chait has been continuously funded by the NIH and other sources to study mechanisms of atherogenesis, with a particular focus on the role of diabetes in the pathogenesis of macrovascular disease. He has served as Director of the UW’s Clinical Nutrition Research Unit (CNRU) – recently renamed Nutrition Obesity Research Center (NORC) since 1992, is a PI for a Program Project to study macrovascular disease in diabetes, is the Project Leader on another Program Project Grant, and is the PI on a NIH T32 Training Grant from the NHLBI. He is a member of the American Society for Clinical Investigation and the Association of American Physicians, and serves on several editorial boards. He also chairs the US-Japan Nutrition and Metabolism Panel of the US-Japan Cooperative Medical Science Program.


Clinical Interest

Dr. Chait’s clinical work focuses on endocrinology care at the UWMC Endocrinology Clinic and treatment of lipid disorders at the HMC Lipid Clinic.


Research Interest

The focus of the laboratory is on investigation of the cell biology of atherosclerosis, with particular emphasis on the roles of atherogenic lipoproteins, diabetes mellitus, and inflammation.  The molecular determinants of lipoprotein retention by extracellular matrix molecules secreted by vascular smooth muscle cells and macrophages is being studied using cell culture techniques, animal models and specimens of human arteries.  An additional aspect of interest relates to how inflammatory signals alter adipocyte biology and lipoprotein composition and function, and how these changes might play a role in atherogenesis.



Publications

Han, C.Y., Kargi, A.Y., Omer, M., Chan, C.K., Wabitsch, M., O’Brien, K.D., Wight, T.N., Chait, A.: Differential effect of saturated and unsaturated free fatty acids on the generation of monocyte adhesion and chemotactic factors by adipocytes: dissociation of adipocyte hypertrophy from inflammation.  Diabetes 59:386-396, 2010.

Yoon, J., Subramanian, S., Ding, Y., Wang, S., Goodspeed, L., Sullivan, B., Kim, J., O’Brien, K., Chait, A.: Chronic insulin therapy reduces adipose tissue macrophage content in LDL-receptor-deficient mice. Diabetologia 54:1252-60, 2011.

Chiba, T., Chang, M., Wang S., Wight T., McMillen T., Oram J., Vaisar T., Heinecke J., DeBeer, F., De Beer, M., Chait, A.: Serum amyloid A facilitates the binding of high-density lipoprotein from mice injected with lipopolysaccharide to vascular proteoglycans. Arterioscler. Thromb. Vasc. Biol., 31:1326-32, 2011.

Subramanian, S., Goodspeed, L., Wang, S., Kim, J., Zeng, L., Ioannou, G., Haigh, W., Yeh, M., Kowdley, K., O’Brien, K., Pennathur, S., Chait, A.: Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice.  J Lipid Res., 52:1626-35. 2011.

Han, C.Y., Umemoto, T., Omer, M., Den Hartigh, L.J., Chiba, T., Leboeuf, R., Buller, C.L., Sweet, I.R., Pennathur, S., Abel, E.D., Chait, A.: NADPH oxidase-derived reactive oxygen species increases expression of monocyte chemotactic factor genes in cultured adipocytes. J. Biol. Chem. 287:10379-93, 2012.

Ding, Y., Subramanian, S., Montes, V., Goodspeed, L., Wang, S., Han, C.Y., Sta. Teresa III, A., Kim, J., O’Brien, K., Chait, A.: Toll-like receptor 4 deficiency decreases atherosclerosis but does not protect against inflammation in obese LDL receptor-deficient mice. Arterioscler. Thromb. Vasc. Biol. 32:1596-1604, 2012.

Umemoto, T., Subramanian, S., Ding, Y., Goodspeed, L., Wang, S., Han, C.Y., Sta. Teresa, A., Kim, J., O’Brien, K., Chait, A.: Inhibition of intestinal cholesterol absorption decreases atherosclerosis but not adipose tissue inflammation. J. Lipid Res. 53:2380-2389, 2012.

Tateya, S., Rizzo-De Leon, N., Handa, P., Cheng, A., Morgan-Stevenson, V., Ogimoto, K., Kanter, J., Bornfeldt, K., Daum, G., Clowes, A., Chait, A., Kim, F.: VASP increases hepatic fatty acid oxidation by activating AMPK in mice. Diabetes. 62:1913-22, 2013.

Umemoto, T., Han, C.Y., Mitra, P., Averill, M., Tang, C., Goodspeed, L., Omer, M., Subramanian, S., Wang, S., den Hartigh, L., Wei, H., Kim, E., Kim, J., O’Brien, K., Chait, A.: Apolipoprotein A-I and HDL have anti-inflammatory effects on adipocytes via cholesterol transporters: ATP-binding cassette (ABC) A-1, ABCG-1 and scavenger receptor B-1(SRB-1). Circ. Res. 112:1345-54, 2013.

Montes, V., Turner, M., Subramanian, S., Ding, Y., Hayden-Ledbetter, M., Slater, S., Goodspeed, L., Wang, S., Omer, M., den Hartigh, L., Averill, M., O’Brien, K., Ledbetter, J., Chait, A.: T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese mice. PLoS ONE 8(7):e67709. doi:10.1371/journal.pone.0067709, 2013.

Subramanian, S., Turner, M., Ding, Y., Goodspeed, L., Wang, S., Buckner, J., O’Brien, K., Getz, G., Reardon, C., Chait, A.: Increased levels of invariant natural killer T lymphocytes worsens metabolic abnormalities and atherosclerosis in obese mice. J. Lipid Res. 54:2831–41, 2013.

den Hartigh, L., Han, C., Wang, S., Omer, M., Chait, A.: 10E, 12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species. J. Lipid Res. 54:2964-78, 2013.