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Research Abstracts Online
January - December 2011

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University of Minnesota Twin Cities
College of Biological Sciences
Medical School
Department of Biochemistry, Molecular Biology, and Biophysics

PI: David A. Bernlohr

Role of Adipocytes in Mammalian Lipid Metabolism

This group examines cytoplasmic fatty acid binding proteins and their role(s) in mediating fatty acid metabolism in adipocytes and macrophages, particularly leukotriene synthesis. Using a combination of biochemical, biophysical, and molecular methodologies, the researchers study the synthesis of inflammatory lipids in macrophages and other cells. Importantly, animal models either null or transgenic for fatty acid binding proteins reveal that intracellular lipid metabolism control the synthesis and secretion of adipose-derived cytokines (adipokines) linked to glucose and lipid metabolism in muscle and liver. Using a drug discovery approach, small molecule inhibitors of FABPs have been identified that exhibit anti-inflammatory properties in macrophages. Such studies provide a framework for the analysis of obesity-linked insulin resistance.

The researchers are also engaging in a major project on oxidative stress and mitochondrial function in adipocytes. Plasma membrane lipids undergo chemical and enzymatic peroxidation leading to the generation of a,b-unsaturated aldehydes such as 4-hydroxynonenal. Such reactive lipids form chemical cross links with proteins and DNA and are implicated in oxidative diseases such as psoriasis, aging, macular degeneration and type 2 diabetes. Moreover, such protein modification, termed carbonylation, leads to system-wide changes in cellular function including mitochondrial respiration and signal transduction. In this project, the researchers examine antioxidant defense systems operable in adipose tissue and their regulation by pro-inflammatory cytokines. Importantly, loss of antioxidant defenses in type 2 diabetes leads to increased protein carbonylation and decreased mitochondrial function. Such mitochondrial dysfunction may underlie many of the biochemical events linked to insulin resistance and lead to new insight in age and nutrient-dependent diseases.

Group Members

Joel S. Burrill, Staff
Jessica Curtis, Graduate Student
Rocio Foncea, Research Associate
Brigette Frohnert, Faculty Collaborator
Candace A. Gename, Staff
Wendy Hahn, Staff
Anna Kristina Hellberg, Graduate Student
Ann Hertzel, Research Associate
Jacob J. Inda, Undergraduate Student
Geraldine Larson, Staff
Marissa Lee, Undergraduate Student
Bruce Witthuhn, Research Associate