Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/10/2010
Publication Date: 11/21/2010
Citation: Picklo, M.J., Uthus, E.O. 2010. Methionine sulfoxide disposition Is altered in animal models of obesity [Abstract]. Society for Free Radical Biology and Medicine. No. 80. p. S40.
Technical Abstract: Over 20% of populations in western countries are obese. Recently, two genetic studies indicate that the MSRA locus, containing the gene for the enzyme methionine sulfoxide reductase A (MsrA), is positively linked to the development of visceral adiposity. MsrA catalyzes the repair of methionyl thiol residues that are oxidized to sulfoxides by hydrogen peroxide. In cells, Msr activity is comprised of two functional enzyme classes, MsrA (reducing methionine-S-sulfoxide) and MsrB (reducing methionine-R-sulfoxide). Importantly, the methionine sulfoxide (MESO) modification of proteins is a redox switch that alters intracellular signaling and protein-protein interactions. In this work, we tested the hypotheses that obesity reduces Msr activity and increases MESO protein levels. We utilized two rat models of obesity, diet-induced obesity (DIO) and the Zucker obese rat, and studied liver, visceral adipose and subcutaneous adipose tissues. MsrA activity was significantly lower in the visceral adipose tissue in the DIO (28% decrease) and the Zucker rat (25% decrease) versus controls. MsrB activity was significantly lower (23%) in the visceral adipose of the Zucker rat versus controls. On the other hand, there were no changes in MsrA or MsrB activities in liver between the obese and control groups. Immunoblot analysis demonstrated no changes in MsrA protein content as a result of obesity in any tissue although liver contained significantly higher levels of MsrA than adipose. Using immunoblot analysis with anti-MESO antibodies, we observed that only select proteins have MESO modifications. While levels of MESO proteins did not change in adipose tissue as a result of obesity, levels of hepatic MESO proteins were significantly reduced (35%-40%) in the Zucker and DIO models versus controls. Subcellular fractionation studies in liver from DIO rats indicate that the cytosol and microsomal fractions contained the major MESO proteins. Our data indicate that obesity changes the content of MESO proteins, the activities of Msr enzymes, and likely, MESO-based redox regulation of cellular function.