Pretreatment with n-6 PUFA protects against subsequent high fat diet induced atherosclerosis—Potential role of oxidative stress-induced antioxidant defense

Abstract

Objectives Recent evidence suggests that oxidative stress can promote antioxidant defense and thus be athero-protective. n-6 Polyunsaturated fatty acids (n-6 PUFA) are more prone to oxidation, compared to monounsaturated fatty acids (MUFA) and yet have proven anti-atherosclerotic effects. In this study, we tested whether early exposure to a diet rich in n-6 PUFA, compared to a MUFA rich diet would reduce lesion burden, even with subsequent exposure to a high fat, high cholesterol diet (HF). Further, we tested to determine whether oxidative mechanisms are involved in such protection. Methods and Results Twenty four, 4 week old, male, LDL receptor knockout (LDL-R−/−) mice were divided into two groups and fed either a n-6 PUFA rich or a MUFA rich diet for a period of 12 weeks. At this point, 4 mice from each group were euthanized and the remaining 8 mice from each group were fed a HF diet for four weeks. Atherosclerotic lesions, plasma lipids, autoantibodies to lipid peroxide modified proteins, isoprostanes and aortic catalase levels were measured. The n-6 PUFA diet reduced aortic lesions and plasma lipids compared to the MUFA diet and this reduction in lesions continued even after the mice were switched over to the HF diet, despite the fact that the plasma lipids were similar in both groups after the HF diet. n-6 PUFA fed mice had highest plasma isoprostane levels, indicating oxidative stress, but also had higher levels of aortic catalase. On the other hand, MUFA fed mice had comparatively lower levels of isoprostanes and their aortic catalase levels remained low. Finally, aortic lesions were negatively correlated with isoprostanes and catalase. Conclusion An initial exposure to a n-6 PUFA rich diet compared to a MUFA rich diet reduces atherosclerotic lesions and this protection probably involves oxidative stress induced by PUFA.

Resveratrol improves high-fat diet induced insulin resistance by rebalancing subsarcolemmal mitochondrial oxidation and antioxidantion

“…SS mitochondria, localized just beneath the sarcolemmal membrane [18], may be more susceptible to damage by HFD-induced increased fatty acid, because lipid content decreases exponentially from immediately below the sarcolemma toward the central region of the muscle fiber [26]. In addition, distinct stages in the progression of the pathophysiology of mitochondrial damage induced by dietary changes might range from initial adaptive to more chronic maladaptive changes [8,21]. Therefore, we speculate that IMF mitochondria may be at a compensatory state after 8 weeks HFD in our study.…”

Chemical composition and antimicrobial activity of Hyptis suaveolens Poit. seed oil from Uttarakhand State, India

“…In another study, Agoramoorthy et al (2007) proved that Fatty acid Methyl Esters (FAME) from Excoecaria agallocha L. that was detrimental to Bacillus subtilis and S. aureus (MIC: 0.125 mg/ml) contained less of linoleic and oleic acids (3.13 and 1.71 %) ) and more of palmitic acid (56.02 %) when compared to our study. It has been proved that unsaturated fatty acids (especially PUFAs) help to reduce cholesterol formation or deposition and hence to decrease the risks of atherosclerosis and other heart disease (Penumetcha et al 2012). The susceptibility of Gram positive bacteria to H. suaveolans oil compared to Gram negative species might be due to the presence of hydrophilic outer membrane in the latter, mainly with regard to the presence of lipoproteins and lipopolysaccharides in the cell wall which form a barrier to hydrophobic compounds.…”

Long‐Term Measures of Dyslipidemia, Inflammation, and Oxidative Stress in Rats Fed a High‐Fat/High‐Fructose Diet

“…In the majority of studies, only F2-isoprostane or 8-isoprostane was measured by ELISA in blood or urine and seldom in tissues, which gave often discordant results. These studies have reported either increased (Zhu et al, 2008) or unchanged or (Petersson et al, 2010) even decreased (Penumetcha et al, 2012) isoprostane levels with HF or HF/HS diets in human or rodent models.…”