Dietary Omega-3 Fatty Acids Do Not Change Resistance of Rat Brain or Liver Mitochondria to Ca(2+) and/or Prooxidants.

Irina G Stavrovskaya,Heather K Greenberg,Susan S Bird,Caryn L Porter,Vasant R Marur,Bruce S Kristal,Sergei V Baranov

doi:10.1155/2012/797105

Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) block apoptotic neuronal cell death and are strongly neuroprotective in acute and chronic neurodegeneration. Theoretical considerations, indirect data, and consideration of parsimony lead to the hypothesis that modulation of mitochondrial pathway(s) underlies at least some of the neuroprotective effects of n-3 PUFAs. We therefore systematically tested this hypothesis on healthy male FBFN1 rats fed for four weeks with isocaloric, 10% fat-containing diets supplemented with 1, 3, or 10% fish oil (FO). High resolution mass spectrometric analysis confirmed expected diet-driven increases in docosahexaenoic acid (DHA, 22:6, n-3) and eicosapentaenoic acid (EPA, 20:5, n-3) in sera, liver and nonsynaptosomal brain mitochondria. We further evaluated the resistance of brain and liver mitochondria to Ca2+ overload and prooxidants. Under these conditions, neither mitochondrial resistance to Ca2+ overload and prooxidants nor mitochondrial physiology is altered by diet, despite the expected incorporation of DHA and EPA in mitochondrial membranes and plasma. Collectively, the data eliminate one of the previously proposed mechanism(s) that n-3 PUFA induced augmentation of mitochondrial resistance to the oxidant/calcium-driven dysfunction. These data furthermore allow us to define a specific series of follow-up experiments to test related hypotheses about the effect of n-3 PUFAs on brain mitochondria.

Highlights

In mammals, the central nervous system (CNS) has the second highest concentration of lipids after adipose tissue
LC-MS grade acetonitrile (ACN), methanol (MeOH), and isopropanol (IPA), as well as high-performance liquid chromatography (HPLC) grade dichloromethane (DCM) and dimethyl sulfoxide were purchased from Fisher Scientific (Pittsburg, PA) and ammonium formate was purchased from SigmaAldrich
The results from our pilot study demonstrate that four weeks of dietary supplementation with 1, 3, or 10% fish oil (FO) enriched with an essential n-3 fatty acids EPA and DHA induced the expected significant changes in plasma and mitochondrial membrane fatty acid composition

Summary

Introduction

The central nervous system (CNS) has the second highest concentration of lipids after adipose tissue. One of the main constituents of brain phospholipids is the omega-3 group of polyunsaturated fatty acids (n-3 PUFAs). DHA (22:6, n-3), the longest and most unsaturated fatty acid, is an essential n-3 PUFA for brain—it is highly enriched in neural membranes, constituting 30–40% of phospholipids in the cerebral cortex and retina [3, 4]. Because brain tissue is unable to make n-3 PUFAs, it is remarkably sensitive to adequate diet supplementation during all stages of CNS development—from embryonic differentiation to adulthood and aging [2, 4,5,6,7]. Neural trauma and neurodegeneration are associated with significant disturbances in neuronal membrane phospholipid metabolism [8,9,10], suggesting that supplementation with n-3 PUFAs may be beneficial for recovery

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