Markers of neuroprotection of combined EPA and DHA provided by fish oil are higher than those of EPA (Nannochloropsis) and DHA (Schizochytrium) from microalgae oils in Wistar rats

BackgroundTo overcome the current overexploitation of fish rich in n-3 long chain polyunsaturated fatty acids (LCPUFA), microalgae have become a promising marine lipid source. The purpose of this study was to assess eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), isolated or combined from distinct marine origins, on the promotion of neuroprotective effects.MethodsThe experiment lasted for 10 weeks and involved 32 Wistar rats, divided into 4 diets (n = 8): a diet rich in milk fat was taken as control (Milk Fat) and compared to n-3 LCPUFA enriched diets, either in EPA + DHA form through fish oil (Fish Oil), or EPA through Nannochloropsis oil (Nanno), or DHA through Schizochytrium oil (Schyzo), while maintaining Milk Fat incorporation.ResultsPlasma lipid profile and dopamine levels were more beneficial in Fish Oil diet. In addition, n-3 LCPUFA incorporation was found increased in liver and erythrocytes from Fish Oil fed rats, suggesting that fish oil is a better dietary source for fatty acids deposition in the organism than microalgae. The Forced Swimming Test revealed a positive behavioural action of EPA + DHA, in opposition to Milk Fat and Nanno diets, which had higher immobile times. mRNA levels of serotonin receptors, HT1A and HT2A along with CREB, the transmission factor for learning and memory, were higher in the hippocampus of rats fed n-3 LCPUFA diets comparative to Milk Fat.ConclusionTaken together, the combination of EPA and DHA from fish oil can counteract the undesirable health effects of saturated fat based diets and benefit, in the long run, neurological function.

[1]  A. Simopoulos An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity , 2016, Nutrients.

[2]  P. Schenk,et al.  Towards sustainable sources for omega-3 fatty acids production. , 2014, Current opinion in biotechnology.

[3]  A. Minihane,et al.  Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C]α-linolenic acid to longer-chain fatty acids and partitioning towards β-oxidation in older men , 2003, British Journal of Nutrition.

[4]  D. Harman The aging process. , 1988, Basic life sciences.

[5]  J. Schwacke,et al.  Fatty acids differentially regulate insulin resistance through endoplasm reticulum stress-mediated induction of tribbles homologue 3: a potential link between dietary fat composition and the pathophysiological outcomes of obesity , 2013, Diabetologia.

[6]  A. Michael-Titus,et al.  Neurological Benefits of Omega-3 Fatty Acids , 2008, NeuroMolecular Medicine.

[7]  R. Wurtman A Nutrient Combination that Can Affect Synapse Formation , 2014, Nutrients.

[8]  E. Bouzinova,et al.  The importance of n-6/n-3 fatty acids ratio in the major depressive disorder. , 2016, Medicina.

[9]  J. Schneider,et al.  Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease. , 2012, Journal of Alzheimer's disease : JAD.

[10]  Steven Finkbeiner,et al.  Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism , 1998, Neuron.

[11]  A. Sukenik,et al.  Effects of the Marine Unicellular Alga Nannochloropsis sp. to Reduce the Plasma and Liver Cholesterol Levels in Male Rats Fed on Diets with Cholesterol , 2003, Bioscience, biotechnology, and biochemistry.

[12]  J. Lumsden Clinical Biochemistry of Domestic Animals. , 1998 .

[13]  R. Porsolt,et al.  Depression: a new animal model sensitive to antidepressant treatments , 1977, Nature.

[14]  S. Carlson,et al.  Decreased brain docosahexaenoic acid content produces neurobiological effects associated with depression: Interactions with reproductive status in female rats , 2008, Psychoneuroendocrinology.

[15]  F. Speleman,et al.  Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes , 2002, Genome Biology.

[16]  D. Mozaffarian,et al.  (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? , 2012, The Journal of nutrition.

[17]  C. Akoh,et al.  EFFECTS OF STRUCTURED LIPID CONTAINING OMEGA‐3 AND MEDIUM CHAIN FATTY ACIDS ON SERUM LIPIDS AND IMMUNOLOGICAL VARIABLES IN MICE , 1999 .

[18]  A. Hofman,et al.  Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk. , 2009, The American journal of clinical nutrition.

[19]  P. Calder Fatty acids and inflammation: the cutting edge between food and pharma. , 2011, European journal of pharmacology.

[20]  N. Bandarra,et al.  Seasonal Changes in Lipid Composition of Sardine (Sardina pilchardus) , 1997 .

[21]  P. Bozzatello,et al.  Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data , 2016, Journal of clinical medicine.

[22]  R. Gibson,et al.  Dietary polyunsaturated fatty acids and inflammatory mediator production. , 2000, The American journal of clinical nutrition.

[23]  G. Barceló-Coblijn,et al.  Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: benefits for human health and a role in maintaining tissue n-3 fatty acid levels. , 2009, Progress in lipid research.

[24]  H. Soininen,et al.  Fat intake at midlife and cognitive impairment later in life: a population‐based CAIDE study , 2008, International journal of geriatric psychiatry.

[25]  M. L. Taylor,et al.  Stearidonic Acid-Enriched Soybean Oil Increased the Omega-3 Index, an Emerging Cardiovascular Risk Marker , 2008, Lipids.

[26]  N. Bandarra,et al.  Seasonal variation in the chemical composition of horse-mackerel (Trachurus trachurus) , 2001 .

[27]  Yongsoon Park,et al.  N-3 polyunsaturated fatty acid consumption produces neurobiological effects associated with prevention of depression in rats after the forced swimming test. , 2012, The Journal of nutritional biochemistry.

[28]  S. Tufik,et al.  Chronic ω-3 fatty acids supplementation promotes beneficial effects on anxiety, cognitive and depressive-like behaviors in rats subjected to a restraint stress protocol , 2011, Behavioural Brain Research.

[29]  C. Thomsen,et al.  Evaluation of total lipids using enzymatic methods for the normalization of persistent organic pollutant levels in serum. , 2006, The Science of the total environment.

[30]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

[31]  P. Calder Mechanisms of action of (n-3) fatty acids. , 2012, The Journal of nutrition.

[32]  P. Guesnet,et al.  Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations. , 2011, Biochimie.

[33]  F. Gomez-Pinilla,et al.  Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. , 2004, Journal of neurotrauma.

[34]  F. Russell,et al.  Distinguishing Health Benefits of Eicosapentaenoic and Docosahexaenoic Acids , 2012, Marine drugs.

[35]  R. Winwood Recent developments in the commercial production of DHA and EPA rich oils from micro-algae , 2013 .

[36]  R. Bazinet,et al.  β-oxidation and rapid metabolism, but not uptake regulate brain eicosapentaenoic acid levels. , 2015, Prostaglandins, leukotrienes, and essential fatty acids.

[37]  D. Harman,et al.  The aging process. , 1981, Basic life sciences.

[38]  Michael W Pfaffl,et al.  RNA integrity and the effect on the real-time qRT-PCR performance. , 2006, Molecular aspects of medicine.

[39]  K. Kristensson,et al.  Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease , 1991, Lipids.

[40]  J. Kaneko Clinical biochemistry of domestic animals , 1963 .

[41]  Claus Lindbjerg Andersen,et al.  Normalization of Real-Time Quantitative Reverse Transcription-PCR Data: A Model-Based Variance Estimation Approach to Identify Genes Suited for Normalization, Applied to Bladder and Colon Cancer Data Sets , 2004, Cancer Research.

[42]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[43]  T. Dinan,et al.  N-3 Polyunsaturated Fatty Acids through the Lifespan: Implication for Psychopathology , 2016, The international journal of neuropsychopharmacology.

[44]  D. Guilloteau,et al.  Dietary fish oil affects monoaminergic neurotransmission and behavior in rats. , 1998, The Journal of nutrition.

[45]  S. Rapoport,et al.  Docosahexaenoic acid (DHA) incorporation into the brain from plasma, as an in vivo biomarker of brain DHA metabolism and neurotransmission. , 2011, Prostaglandins & other lipid mediators.

[46]  J. Bradbury Docosahexaenoic Acid (DHA): An Ancient Nutrient for the Modern Human Brain , 2011, Nutrients.

[47]  C. Serhan,et al.  Resolvins and protectins in inflammation resolution. , 2011, Chemical reviews.

[48]  R. Bazinet,et al.  The effect of linoleic acid on the whole body synthesis rates of polyunsaturated fatty acids from α-linolenic acid and linoleic acid in free-living rats. , 2016, The Journal of nutritional biochemistry.

[49]  N. Bandarra,et al.  Docosahexaenoic acid at the sn-2 position of structured triacylglycerols improved n-3 polyunsaturated fatty acid assimilation in tissues of hamsters. , 2016, Nutrition research.

[50]  L. Trabace,et al.  Maternal Malnutrition in the Etiopathogenesis of Psychiatric Diseases: Role of Polyunsaturated Fatty Acids , 2016, Brain sciences.

[51]  Kaia Palm,et al.  Mouse and rat BDNF gene structure and expression revisited , 2006, Journal of neuroscience research.

[52]  D. Ma,et al.  Experimental models and mechanisms underlying the protective effects of n-3 polyunsaturated fatty acids in Alzheimer's disease. , 2009, The Journal of nutritional biochemistry.

[53]  Siddharth Gaikwad,et al.  The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer's disease: Acting separately or synergistically? , 2016, Progress in lipid research.

[54]  R. Berge,et al.  Modulation of plasma and hepatic oxidative status and changes in plasma lipid profile by n-3 (EPA and DHA), n-6 (corn oil) and a 3-thia fatty acid in rats. , 1994, Biochimica et biophysica acta.

[55]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[56]  John M. Davis,et al.  Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73) , 2016, British Medical Journal.

[57]  C. N. Pederiva,et al.  ETHOWATCHER: validation of a tool for behavioral and video-tracking analysis in laboratory animals , 2012, Comput. Biol. Medicine.

[58]  I. G. Fantus,et al.  In vivo effects of polyunsaturated, monounsaturated, and saturated fatty acids on hepatic and peripheral insulin sensitivity. , 2015, Metabolism: clinical and experimental.

[59]  G. Duchateau,et al.  Age dependent incorporation of 14C-DHA into rat brain and body tissues after dosing various 14C-DHA-esters. , 2010, Prostaglandins, leukotrienes, and essential fatty acids.

[60]  C. Caltagirone,et al.  n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice , 2014, Front. Aging Neurosci..

[61]  F. Visioli,et al.  Differential distribution of DHA-phospholipids in rat brain after feeding: A lipidomic approach. , 2011, Prostaglandins, leukotrienes, and essential fatty acids.

[62]  R. Bazinet,et al.  Effect of dietary docosahexaenoic acid (DHA) in phospholipids or triglycerides on brain DHA uptake and accretion. , 2016, The Journal of nutritional biochemistry.

[63]  E. Mannarino,et al.  The endocrine function of adipose tissue: an update , 2006, Clinical endocrinology.

[64]  Tad T. Brunyé,et al.  Omega-3 fatty acids and stress-induced changes to mood and cognition in healthy individuals , 2015, Pharmacology Biochemistry and Behavior.

[65]  Simon C. Dyall,et al.  Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA , 2015, Front. Aging Neurosci..

[66]  J. Klenk,et al.  Changes in life expectancy 1950–2010: contributions from age- and disease-specific mortality in selected countries , 2016, Population Health Metrics.

[67]  L. G. Ensminger The Association of Official Analytical Chemists , 1976 .

[68]  Colin Ratledge,et al.  Fatty acid biosynthesis in microorganisms being used for Single Cell Oil production. , 2004, Biochimie.

[69]  A. Logan Neurobehavioral aspects of omega-3 fatty acids: possible mechanisms and therapeutic value in major depression. , 2003, Alternative medicine review : a journal of clinical therapeutic.

[70]  S. Rapoport,et al.  Brain lipid concentrations in bipolar disorder. , 2010, Journal of psychiatric research.

[71]  F. Marangoni,et al.  n-3 fatty acids: functional differences between food intake, oral supplementation and drug treatments. , 2013, International journal of cardiology.

[72]  S. Heinrichs Dietary omega-3 fatty acid supplementation for optimizing neuronal structure and function. , 2010, Molecular nutrition & food research.

[73]  S. Rapoport,et al.  Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liver. , 2007, Prostaglandins, leukotrienes, and essential fatty acids.

[74]  M. Muscaritoli,et al.  The Role for Dietary Omega-3 Fatty Acids Supplementation in Older Adults , 2014, Nutrients.