Page Banner

United States Department of Agriculture

Agricultural Research Service

Research Project: FOOD FACTORS AND MAINTENANCE OF BODY WEIGHT AND HEALTH Title: Obesity reduces methionine sulfoxide reductase activity in visceral adipose tissue

Authors
item Uthus, Eric
item PICKLO, MATTHEW

Submitted to: Free Radical Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 24, 2011
Publication Date: July 5, 2011
Repository URL: http://handle.nal.usda.gov/10113/56927
Citation: Uthus, E.O., Picklo, M.J. 2011. Obesity reduces methionine sulfoxide reductase activity in visceral adipose tissue. Free Radical Research. 45(9):1052-1060.

Interpretive Summary: Obesity is linked to the development of insulin resistance and cardiovascular disease. Elevated levels of oxidative stress are observed in obese individuals and in animal models of obesity, pointing to a mechanistic role of oxidative stress. A recent genetic study indicated that the gene for the anti-oxidant defense enzyme methionine sulfoxide reductase A (MsrA) is positively associated with the development of visceral obesity (obesity in the body cavity). In this work, we tested the hypothesis that Msr activity is diminished in visceral fat as a result of obesity. We used two animal models of obesity, wild-type rats fed a high-fat diet and genetically obese rats (Zucker rats). Our data indicate that multiple forms of methionine sulfoxide activity are reduced in the visceral fat stores but not in the liver or subcutaneous fat in both obesity models. Analysis of methionine sulfoxide (METO)-modified proteins indicated a decrease in liver METO proteins in the obese animals with no changes in visceral fat. On the other hand a novel METO protein was observed in the subcutaneous fat of the Zucker rat. Our data indicate that anti-oxidant enzyme activity is diminished in obese animals and that the Msr/METO pathway may play a role in the oxidative stress signaling of obesity.

Technical Abstract: Visceral obesity is linked to the development of comorbidities including insulin resistance and cardiovascular disease. Elevated levels of oxidative stress are observed in obese individuals and in animal models of obesity, pointing to a mechanistic role of oxidative stress. A recent genetic study indicated that the gene locus for the anti-oxidant defense enzyme methionine sulfoxide reductase A (MsrA) is positively associated with the development of visceral adiposity. In this work, we tested the hypothesis that Msr activity is diminished in visceral fat as a result of obesity. We used two animal models of obesity, wild-type rats fed a high-fat (45% of calories from fat) diet and Zucker rats fed a 10% fat calorie diet. Our data indicate that MsrA activity was selectively reduced approximately 25% in the visceral adipose, but not subcutaneous adipose or liver, of both rat models as compared to control, wild type rats receiving a 10% fat calorie diet. Furthermore, MsrB activity was similarly reduced only in visceral fat. There were no differences in MsrA protein content in any of these three tissues indicating a loss in the specific activity of the enzyme. A decrease in MsrB1 protein was observed in peri-renal adipose. Analysis of methionine sulfoxide (METO)-modified proteins indicated a decrease in hepatic METO proteins in the obese animals with no changes in peri-renal adipose. On the other hand a novel METO protein was observed in the subcutaneous adipose of the Zucker rat. Our data indicate that Msr activity is diminished in obese animals and that the Msr/METO pathway may play a role in the oxidative stress signaling of obesity.

Last Modified: 7/28/2014
Footer Content Back to Top of Page