Original Research ArticleStearidonic acid combined with alpha-linolenic acid improves lipemic and neurological markers in a rat model subject to a hypercaloric diet
Introduction
In the recent decades, the importance of dietary fat in the human diet as a decisive factor for health has been established [1]. In particular, n-3 very long chain polyunsaturated fatty acids (VLCPUFAs, > C18), especially eicosapentaenoic (EPA, 20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) acids, have been ascribed a wide array of beneficial health effects [1]. Various epidemiological studies point out the importance of n-3 VLCPUFA in the prevention of cardiovascular mortality due to myocardial infarction, cardiac arrest, sudden death or stroke [2], [3]. The effects may be related to alterations in tissue lipid composition, cell membrane FAs, and derived lipid mediators production, which are anti-inflammatory in the case of n-3 VLCPUFA [4]. Moreover, the consumption of large amounts of n-3 VLCPUFA, particularly DHA, has been ascribed a positive impact on the nervous system, thereby reducing the risk of depression [5] and mood and behavior disorders [6], [7].
Fish oil is rich in n-3 VLCPUFA. However, the amount of fish oil necessary to obtain high concentrations of these FAs in the blood in order to ensure therapeutic benefits may be larger than the amounts provided by Western diets. In addition, fish oil production exerts an additional pressure on the already overexploited marine resources. Accordingly, alternative n-3 PUFA-containing sources must be assessed. Typically, terrestrial plants rich in n-3 PUFA have α-linolenic acid (ALA, 18:3 n-3) and stearidonic acid (SDA, 18:4 n-3). Therefore, these two n-3 LCPUFA are worth assessing, including their possible conversion into n-3 VLCPUFA. SDA is the least studied FA regarding this subject.
It may be possible that EPA and DHA may be biosynthesized in the human body using ALA and SDA as starting substrates. However, for healthy and non-vegetarian humans the synthesis of n-3 VLCPUFA in adults is extremely limited [8], [9]. Even with a diet deficient in DHA, the cells’ ability to synthesize DHA from ALA is very low [10]. One study indicates a very low share of plasma ALA, < 0.2%, deployed to the synthesis of DHA via EPA [8]. Indeed, it has been claimed an extremely low conversion of the precursor ALA to EPA, < 5% [11], and to DHA, < 0.05% [12].
Evidence is emerging that another C18 n-3 LCPUFA, SDA —an intermediate metabolite between ALA and EPA—, is more efficiently converted to EPA in the body than ALA [13], [14] and may therefore be better than ALA to enhance n-3 VLCPUFA levels. Besides seafood, some foods have been identified to be comparatively rich in SDA, namely, seeds from plants of the Boraginaceae family, including Buglossoides arvensis [15], [16]. As practical application, feed enriched in SDA was more efficient at increasing tissue n-3 VLCPUFA than feed with incorporated ALA in broiler chickens [17]. In contrast, other studies did not observe any increase of the DHA levels as a result of SDA supplementation [18]. Therefore, this aspect needs to be clarified.
In this study, on the basis of the possibility of converting ALA and SDA to EPA and DHA, it is hypothesized that plants rich in ALA and SDA can counteract the undesirable health effects of a hypercaloric diet based on milk fat (typical Western diet). The confirmation of this hypothesis would entail that parameters associated to the lipemic and neurological function of Wistar rats (plasma metabolites, FA profiles in relevant tissues, serotonin and catecholamines, inflammation, specific hippocampus gene expression, and animal behavior) are changed by diets rich in ALA and SDA to an extent comparable to what may be achieved by diets enriched in EPA + DHA, as in fish oil.
Section snippets
Ethics statement
The experimental procedures were reviewed by the Ethics Commission of CIISA/FMV and approved by the Animal Care Committee of the National Veterinary Authority (Direcção-Geral de Alimentação e Veterinária, Portugal), in compliance with European Union legislation (2010/63/EU Directive).
Experimental diets
Experimental diets were formulated at CEIA3-Universidad de Almería facilities (Service of Experimental Diets, http://www.ual.es/stecnicos_spe). Four experimental diets were tested: a negative control diet (Ctl)
Animal body composition
The average weights of the animals of each group at the beginning and at the end of the study, the total and daily feed intake in each group (averaged) and the tissues and carcass weights after euthanasia are shown in Table 3.
There were no differences among the studied groups (Ctl, FO, LIN, BUG), except for heart weight. This means that replacing milk fat by ALA or (SDA + ALA)-rich Buglossoides did not produce any negative effect on rat growth and development.
Plasma metabolites
The plasma metabolites are
Discussion
The current study produced a substantial array of results, which need to be analyzed and pondered on the basis of their statistical basis and articulation between them. Accordingly, the Discussion prioritizes the most meaningful results.
Author contributions
JLM, SM, PAL and JC performed experimental work concerning the in vivo trial and associated analyses, RMP performed the blood analyses, PAL was involved in the conduction of the trial, CA and NMB dealt with the analysis of lipids, FJA and MJGF were involved in the determination of health parameters, CC processed the data and wrote the manuscript, JAP coordinated the in vivo trial and some laboratory analysis, and JLGG took care of the overall coordination of the study.
Conflict of interest
No conflict of interest involving any of the authors.
Acknowledgment
This work was supported by the Spanish Ministry of Economy and Competitiveness (project AGL2015-67528-R), and the following Post Doctoral Grants: Ref.: SFRH/BPD/102689/2014 (“Fundação para a Ciência e a Tecnologia”, FCT) for CC; Ref.: SFRH/BPD/64951/2009 (FCT) and DIVERSIAQUA (MAR2020) for CA. PAL is a researcher from Incentivo 2014 project (AGR/UI0276/2014). The authors acknowledge Clínica Médica e Diagnóstico Dr Joaquim Chaves (Algés, Portugal) for the technical assistance regarding the
References (59)
- et al.
n-3 Fatty acids from fish or fish-oil supplements, but not α-linolenic acid, benefit cardiovascular disease outcomes in primary —and secondary— prevention studies: a systematic review
Am. J. Clin. Nutr.
(2006) - et al.
The opposing effects of n-3 and n-6 fatty acids
Prog. Lipid Res.
(2008) - et al.
Considerations regarding neuropsychiatric nutritional requirements for intakes of omega-3 highly unsaturated fatty acids
Prostaglandins Leukot Essent Fatty Acids
(2009) - et al.
Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: A randomized controlled trial
Nutrition
(2012) - et al.
Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans
J. Lipid Res.
(2001) - et al.
Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids
Am. J. Clin. Nutr.
(2003) - et al.
Effects of duration of treatment and dosage of eicosapentaenoic acid and stearidonic acid on red blood cell eicosapentaenoic acid content
Prostaglandins Leukot Essent Fatty Acids
(2012) - et al.
Stearidonic acid as a supplemental source of ω3-polyunsaturated fatty acids to enhance status for improved human health
Nutrition
(2013) - et al.
Optimization of a nitrogen analyser based on the Dumas method
Anal Chim Acta
(2004) - et al.
A simple method for the isolation and purification of total lipids from animal tissues
J. Biol. Chem.
(1957)
Evaluation of total lipids using enzymatic methods for the normalization of persistent organic pollutant levels in serum
Sci. Total Environm.
ETHOWATCHER: validation of a tool for behavioral and video-tracking analysis in laboratory animals
Comp. Biol. Med.
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method
Methods
RNA integrity and the effect on the real-time qRT-PCR performance
Mol. Asp. Med.
Experimental models and mechanisms underlying the protective effects of n-3 polyunsaturated fatty acids in Alzheimer's disease
J. Nutr. Biochem.
Dietary omega-3 fatty acid, ratio of omega-6 to omega-3 intake, inflammation, and survival in long-term hemodialysis patients
Am. J. Kidney Dis.
In vivo effects of polyunsaturated, monounsaturated, and saturated fatty acids on hepatic and peripheral insulin sensitivity
Met. Clin. Exp.
Docosahexaenoic acid at the sn-2 position of structured triacylglycerols improved n-3 polyunsaturated fatty acid assimilation in tissues of hamsters
Nutr. Res.
Whole body synthesis rates of DHA from α-linolenic acid are greater than brain DHA accretion and uptake rates in adult rats
J. Lipid Res.
Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids
Prostaglandins Leukot Essent Fatty Acids
Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liver
Prostaglandins Leukot Essent Fatty Acids
Dietary supplementation of α-linolenic acid induced conversion of n-3 LCPUFAs and reduced prostate cancer growth in a mouse model
Lipids Health Dis.
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
Prog. Lipid Res.
The omega-3 index: A new risk factor for death from coronary heart disease
Prev. Med.
Effect of a linseed diet on lipid oxidation, fatty acid composition of muscle, perirenal fat, and raw and cooked rabbit meat
Meat Sci.
Omega-3 fatty acids and stress-induced changes to mood and cognition in healthy individuals
Pharmacol. Biochem. Behav.
Fatty acids and inflammation: The cutting edge between food and pharma
Eur. J. Pharmacol.
Mechanisms of action of (n-3) fatty acids
J. Nutr.
n-3 Fatty acids and cardiovascular disease: evidence explained and mechanisms explored
Clin. Sci.
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