Skip to main content
ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #276812
Title: S-Glutathionylation of hepatic and visceral adipose proteins decreases in obese rats

Author
item Picklo, Matthew
item Idso, Joseph
item Jackson, Matthew

Submitted to: Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/4/2012
Publication Date: 2/5/2013
Citation: Picklo, M.J., Idso, J.P., Jackson, M.I. 2013. S-Glutathionylation of hepatic and visceral adipose proteins decreases in obese rats. Obesity. 21:297-305.

Interpretive Summary: A number of clinical and biochemical studies demonstrate that obesity and insulin resistance are associated with increases in oxidative stress and inflammation. Paradoxically, insulin sensitivity can be reduced and inflammation enhanced if there is too little oxidative damage to select proteins. In this work, we tested the hypothesis that obesity is associated with decreased levels of proteins containing oxidized protein thiols. We examined tissue levels of specific protein oxidation types, sulfenic acids (PSOH) and glutathione-modified proteins (PSSG) in liver, visceral adipose tissue, and skeletal muscle derived from glucose intolerant, obese-prone Sprague-Dawley rats. Our data indicate that decreases in PSSG content occurred in liver (44%) and adipose (26%) but not skeletal muscle in obese rats fed a 45% fat-calorie diet versus lean rats fed a 10% fat-calorie diet. PSOH content did not change in the tissue between the two groups. The activity of the enzyme glutaredoxin (GLRX) responsible for reversal of PSSG formation did not change in muscle and liver between the two groups. However, levels of GLRX1 were elevated 70% in the adipose tissue of the obese, 45% fat calorie-fed rats. These are the first data to link changes in S-glutathionylation and GLRX1 to adipose tissue in obesity. They also indicate that reduction of certain forms of protein oxidation may be detrimental in obesity. These data also indicate the use of selective antioxidant supplements in obesity people needs more study.

Technical Abstract: A number of clinical and biochemical studies demonstrate that obesity and insulin resistance are associated with increases in oxidative stress and inflammation. Paradoxically, insulin sensitivity can be enhanced by oxidative inactivation of cysteine residues of phosphatases, and inflammation can be reduced by S-glutathionylation with formation of protein-glutathione mixed disulfides (PSSG). Although oxidation of protein-bound thiols (PSH) regulates protein activity and is increased in multiple diseases, it is not known whether there are changes in PSH oxidation species in obesity. In this work, we tested the hypothesis that obesity is associated with decreased levels of proteins containing oxidized protein thiols. We examined tissue levels of protein sulfenic acids (PSOH) and PSSG in liver, visceral adipose tissue, and skeletal muscle derived from glucose intolerant, obese-prone Sprague-Dawley rats. Our data indicate that decreases in PSSG content occurred in liver (44%) and adipose (26%) but not skeletal muscle in obese rats fed a 45% fat-calorie diet versus lean rats fed a 10% fat-calorie diet. PSOH content did not change in the tissue between the two groups. The activity of the enzyme glutaredoxin (GLRX) responsible for reversal of PSSG formation did not change in muscle and liver between the two groups. However, levels of GLRX1 were elevated 70% in the adipose tissue of the obese, 45% fat calorie-fed rats. These are the first data to link changes in S-glutathionylation and GLRX1 to adipose tissue in the obese and demonstrate that redox changes in thiol status occur in adipose tissue as a result of obesity.