Antioxidant supplementation and obesity have independent effects on hepatic oxylipin profiles in insulin resistant, obese-prone rats

Authors: Picklo, Matthew; Newman, John

Submitted to: Free Radical Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/21/2015
Publication Date: 10/1/2015
Publication URL: https://handle.nal.usda.gov/10113/61628
Citation: Picklo, M.J., Newman, J.W. 2015. Antioxidant supplementation and obesity have independent effects on hepatic oxylipin profiles in insulin resistant, obese-prone rats. Free Radical Biology and Medicine. 89:182-191.

Interpretive Summary: Obesity-induced insulin resistance, hyperglycemia, and pre-diabetes are estimated to afflict > 1:5 people in the United States with a cost of over $200B annually. There is controversy as to whether antioxidant supplements, namely vitamin E and vitamin C, may prevent or enhance insulin resistance and hyperglycemia in obese people. In this work, we tested the hypothesis that supplementation with vitamin E and vitamin C prevents glucose intolerance in obese-prone Sprague-Dawley rats. Plasma and tissue indices of antioxidant status, oxidative stress, mitochondrial metabolism, and inflammation were measured. While insulin resistance, fatty liver and adipose inflammation occurred in obese rats vs lean rats, antioxidant supplementation did not prevent these effects in obese rats. Furthermore, mitochondrial dysfunction and oxidative stress did not develop in obese animals. These data suggest that insulin resistance may occur without development of oxidative stress and that supplementation with vitamin E and vitamin C has no impact on preventing insulin resistance and hypglycemia.

Technical Abstract: Objective - Elevated oxidative stress is associated with development of glucose intolerance. In this work, we tested the hypothesis that supplementation with the antioxidants vitamin E (d-alpha-tocopheryl acetate; 0.4 g/kg diet) and vitamin C (0.5 g/kg diet) prevents glucose intolerance in obese-prone Sprague-Dawley rats. Materials/Methods - Rats were fed either a low-fat diet (LF; 10% of energy from fat), a high-fat diet (HF, 45% of energy from fat), or a high-fat diet with supplemented vitamin E and vitamin C (HF-CE). Following 16 weeks on this diet, oral glucose tolerance tests were performed. Plasma and tissue indices of antioxidant status, oxidative stress, and inflammation were measured. Results - While the high-fat diet caused glucose intolerance, antioxidant supplementation did not prevent obesity-induced increases in fasting glucose levels nor prevent obesity-induced increases in the glucose area under the curve. Plasma levels of vitamin E and vitamin C were elevated in the supplemented group. Elevated oxidative stress was not evident in the liver or adipose tissue of the HF rats compared to LF rats nor was there suppression of oxidative damage endpoints with antioxidant supplementation. However, protein-S-glutathionylation was reduced with obesity but not affected by antioxidants. Inflammatory gene expression was elevated in visceral but not subcutaneous adipose. However there was no effect of antioxidant supplementation upon adipose inflammation. Conclusions - These data indicate indices of oxidative damage are not associated with the development of glucose intolerance in the obese-prone rats and that vitamin E and vitamin C supplementation does not prevent glucose intolerance in obese-prone Sprague-Dawley rats.