17 research outputs found
Veldig landkjedede flerumettede fettsyrer og deres biologiske funksjoner
No full textThe overall aim of this thesis was to gain insight into the bioavailability of dietary very-long-chain polyunsaturated fatty acids (VLC-PUFAs) and their potential effects on skin and bone health. While well-known omega-3 (n-3) PUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been extensively studied, less is known about the n-3 VLC-PUFAs, which have chain lengths longer than 24 carbons.
Prior to the work presented in this thesis, VLC-PUFAs were not commercially available in large enough concentrations to supply in feeding trials. Therefore, this thesis is the first study of its kind to conduct dietary feeding trials using VLC-PUFA concentrates in rodents and fish, as well as several in vitro experiments involving n-3 VLC-PUFAs with chain lengths of C24–28. The thesis explores the hypothesis that these VLC-PUFAs have specific tissue functions that are incompletely understood or unknown.
In Paper I, the primary goal was to investigate the bioavailability and distribution of dietary n-3 VLC-PUFAs in various tissues in rat, mice, and Atlantic salmon. The study also assessed whether natural fish oil (FO), rich in long chain precursors to VLCPUFAs, affected tissue VLC-PUFA composition. Rats were fed diets supplemented with natural FO as a source of low dietary levels of n-3 VLC-PUFAs, while Atlantic salmon and mice were fed higher dietary levels of n-3 VLC-PUFAs from a FO concentrate. In all experiments, n-3 VLC-PUFA incorporation into organs was investigated. The results demonstrated that natural FO, which has a high EPA content, increased the endogenous production of n-3 VLC-PUFAs in the eye, skin, and brain of mice to a limited extent, with neglectable amounts of n-3 VLC-PUFA originating from the diet. When higher dietary levels were given in the form of concentrate, these fatty acids were bioavailable and deposited in both the phospholipid and triglyceride fractions of all tissues studied, including skin, eye, brain, testis, liver, and heart, and their distribution appeared to be tissue-dependent but not species-specific. When EPA and DHA were balanced in the diets of Atlantic salmon and n-3 VLC-PUFAs increased, the major n-3 VLC-PUFAs from the concentrate increased significantly in the organs studied. This shows that n-3 VLC-PUFAs can be provided via the diet, and thereby provides a tool for functional studies of these fatty acids.
In paper II, the primary goal was to investigate the potential impact of dietary n-3 VLC-PUFAs on skin health. In this study, Atlantic salmon were fed different dietary levels of n-3 VLC-PUFAs from concentrate during the early parr life stage, a period in which the skin matures and develops. Changes in skin morphology were then analysed at two different time points during the experiment and the effects on skin tissue fatty acid composition was determined. In vitro experiments using human dermal fibroblasts and primary Atlantic salmon keratocytes were also conducted to investigate the effects of VLC-PUFA supplementation on the migration capacity of the cells. The results of the study demonstrated that increasing dietary n-3 VLC-PUFAs led to increased epidermis thickness, higher mucus cell count, and more rapid scale maturation in Atlantic salmon skin in vivo, and thereby a more mature skin morphology and possibly more robust skin, at an earlier life stage. Additionally, the in vitro experiments demonstrated that n-3 VLC-PUFA supplementation resulted in more rapid cell migration, indicating potential beneficial effects of VLC-PUFAs in wound healing.
In paper III, the main goal was to investigate the effects of dietary VLC-PUFAs on bone mineralization. Analysis of fatty acid composition, mineral content, bone density and gene expression after feeding Atlantic salmon increasing dietary levels of n-3 VLCPUFAs from concentrate revealed a positive correlation between increasing dietary n-3 VLC-PUFAs and elevated levels of the minerals phosphorous (P), calcium (Ca), and magnesium (Mg) in both the skin and vertebrae and increased bone mineral density
(BMD). Furthermore, gene expression analysis highlighted potential links between VLC-PUFAs and bone-related processes, with a minimal but noteworthy number of differentially expressed genes related to bone-related processes. In vitro experiments using human foetal osteoblast cells (hFOB 1.19) were also carried out and revealed some trends in the effects of VLC-PUFAs on expression of cytokines and gene expression markers related to bone differentiation. This suggests that the VLC-PUFAs
affected osteoblast differentiation, which aligned with the in vivo findings.
Overall, the work carried out in this thesis demonstrates that VLC-PUFAs can be incorporated into various tissues following dietary supplementation, and that dietary supplementation potentially affects skin maturation and cell migration, with potential implications for wound healing, as well as improving bone mineralization.Hovedmålet med denne avhandlingen var å bidra med kunnskap om biotilgjengeligheten til veldig langkjedede flerumettede fettsyrer (VLC-PUFAs) fra fiskeoljekonsentrat tilført gjennom kosten og deres potensielle effekter på hud- og benhelse. Mens velkjente omega-3 (n-3) PUFAs som eikosapentaensyre (EPA) og dokosaheksaensyre (DHA) har blitt grundig studert, er mindre kjent om n-3 VLCPUFAs med karbonkjeder lengre enn 24 karbonatomer.
Før arbeidet i denne avhandlingen var VLC-PUFAs ikke tilgjengelige i store nok konsentrasjoner for å kunne tilføres i fôringsforsøk. Dette arbeidet er derfor det første av sitt slag, der fôringsforsøk med VLC-PUFA konsentrater ble utført på rotter, mus, og atlantisk laks, samt inkludert i flere in vitro eksperimenter med n-3 VLCPUFAs med kjeder spesifikt mellom C24-28. Avhandlingen utforsker hypotesen om at disse VLC-PUFAene har spesifikke vevsfunksjoner som er ufullstendig forstått eller ukjente.
I artikkel I var det primære målet å undersøke biotilgjengeligheten og fordelingen av n-3 VLC-PUFAs fra kostholdet i ulike vev hos rotter, mus, og atlantisk laks. I tillegg inkluderer studien en undersøkelse av om naturlig fiskeolje (FO), rik på langkjedede forløpere til VLC-PUFAs, påvirker vevssammensetningen av VLC-PUFA. Rotter ble fôret med dietter tilsatt naturlig FO som en kilde til lave kostholdsnivåer av n-3 VLCPUFAs, mens atlantisk laks og mus ble fôret med høyere kostholdsnivåer av n-3 VLCPUFAs fra et FO-konsentrat. I alle fôringsforsøkene ble deponeringen av n-3 VLCPUFAs i organene undersøkt. Resultatene viste at naturlig FO, på grunn av sitt høye EPA-innhold, i begrenset grad økte produksjonen av endogene n-3 VLC-PUFAs i øye, hud, og hjerne hos mus, med ubetydelige mengder n-3 VLC-PUFA som stammet fra kostholdet. Når høyere nivåer ble gitt i kostholdet i form av konsentrat var disse fettsyrene biotilgjengelige og ble deponert i både fosfolipid- (PL) og triglyserid- (TAG) fraksjonene av alle studerte vev og organer, inkludert hud, øye, hjerne, testikler, lever, og hjerte, og deres distribusjon syntes å være vevsavhengig, men ikke arts-spesifikk. Når EPA og DHA var balansert i diettene til atlantisk laks og n-3 VLC-PUFA nivåene økte, økte de viktigste n-3 VLC-PUFAene fra konsentratet signifikant i de undersøkte organene. Dette viser at n-3 VLC-PUFAs kan tilføres gjennom kosthold, og gir dermed et verktøy for funksjonelle studier av disse fettsyrene.
I artikkel II var det primære målet å undersøke den potensielle påvirkningen av kosttilførsel av n-3 VLC-PUFAs på hudhelsen. I denne studien ble atlantisk laks fôret med ulike nivåer av n-3 VLC-PUFAs fra FO-konsentrat i løpet av tidlig parr livsstadiet, en periode hvor huden modnes og utvikler seg. Endringer i hudmorfologi ble deretter analysert ved to ulike tidspunkter i løpet av eksperimentet, og effektene på fettsyresammensetningen av hudvevet ble analysert. Videre ble det utført in vitro eksperimenter med humane dermale fibroblaster og primære keratocytter fra atlantisk laks, for å undersøke effektene av VLC-PUFA tilskudd på migrasjonskapasiteten til cellene. Resultatene viste at økende nivåer av n-3 VLCPUFA førte til økt tykkelse av epidermis, høyere antall slimceller, og raskere modning av skjellene i huden til atlantisk laks in vivo, og dermed en mer moden hudmorfologi og muligens en mer robust hud på et tidligere livsstadium. I tillegg viste in vitro eksperimentene at n-3 VLC-PUFA tilskudd førte til raskere cellemigrasjon, noe som indikerer potensielle gunstige effekter av VLC-PUFA på sårheling.
I artikkel III var det viktigste målet å undersøke effektene av kosttilførsel av n-3 VLCPUFA på benmineralisering. Gjennom analyser av fettsyresammensetning, mineralinnhold og genuttrykk etter fôring av atlantisk laks med økende nivåer av n- 3 VLC-PUFA fra FO-konsentrat i kostholdet, avdekker studien en positiv sammenheng mellom økende nivåer av n-3 VLC-PUFAs og økte nivåer av mineralene fosfor (P), kalsium (Ca) og magnesium (Mg), både i hud og ryggvirvel. Videre peker analysen av genuttrykk på potensielle sammenhenger mellom VLC-PUFAs og benrelaterte prosesser, med et minimalt men signifikant antall gener knyttet til benrelaterte prosesser som var differensielt uttrykt mellom de ulike diettgruppene. In vitro eksperimenter med humane føtale osteoblastceller (hFOB 1.19) ble også utført og viste noen trender i effekter av VLC-PUFA på ekspresjon av cytokiner og genuttrykk av markører knyttet til ben-differensiering. Dette kan indikere at VLC-PUFA påvirker osteoblastdifferensiering, i tråd med in vivo funnene.
Totalt sett har arbeidet utført i denne avhandlingen vist at VLC-PUFAs kan inkorporeres i ulike vev etter tilførsel via kostholdet, og at økt tilførsel gjennom kostholdet potensielt påvirker hudmodning og cellemigrering, med potensielle implikasjoner for sårheling, i tillegg til å forbedre benmineraliseringen.EpaxpublishedVersio
Antioxidant Efficacy of a New Synergistic, Multicomponent Formulation for Fish Oil Omega-3 Concentrates
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Genotoxicity evaluation of a fish oil concentrate containing Very Long Chain Fatty Acids
No full textVery long chain fatty acids (VLCFAs) are lipids found in fish with a chain length longer than C22. They represent a minor lipid fraction composing of less than 1% of the total lipid. EPAX® EVOLVE 05 is a concentrate of VLCFAs providing roughly 10 times the amount found in fish. Here we report genotoxocity studies performed in cell culture and using a rat model. No genotoxicity was noted in a bacterial reverse mutation test (AMES test). An in vitro micronucleus assay was negative with a 4-hr test item incubation but a 24-hr incubation resulted in a positive signal. This prompted further study using an in vivo Sprague Dawley rat model. Test item exposure was demonstrated by plasma measurements from Sprague Dawley rats with peak absorption at 2–4 h post administration, as expected for fatty acids. The micronucleus assay showed no genotoxicity for fish oil containing VLCFAs. Together, the data shows that VLCFAs up to the test dose of 1200 mg/kg b.w. do not show genotoxicity
Toxicological evaluation of a fish oil concentrate containing Very Long Chain Fatty Acids
No full textpublishedVersio
-3 very-long-chain PUFA in different organs of rat, mouse and Atlantic salmon
No full textThere is limited knowledge about the metabolism and function of n-3 very-long-chain PUFA (n-3 VLC-PUFA) with chain lengths ≥ 24. They are known to be produced endogenously in certain tissues from EPA and DHA and not considered to originate directly from dietary sources. The aim of this study was to investigate whether n-3 VLC-PUFA from dietary sources are bio-available and deposited in tissues of rat, fish and mouse. Rats were fed diets supplemented with a natural fish oil (FO) as a source of low dietary levels of n-3 VLC-PUFA, while Atlantic salmon and mice were fed higher dietary levels of n-3 VLC-PUFA from a FO concentrate. In all experiments, n-3 VLC-PUFA incorporation in organs was investigated. We found that natural FO, due to its high EPA content, to a limited extent increased endogenous production of n-3 VLC-PUFA in brain and eye of mice with neglectable amounts of n-3 VLC-PUFA originating from diet. When higher dietary levels were given in the form of concentrate, these fatty acids were bio-available and deposited in both phospholipids and TAG fractions of all tissues studied, including skin, eye, brain, testis, liver and heart, and their distribution appeared to be tissue-dependent, but not species-specific. When dietary EPA and DHA were balanced and n-3 VLC-PUFA increased, the major n-3 VLC-PUFA from the concentrate increased significantly in the organs studied, showing that these fatty acids can be provided through diet and thereby provide a tool for functional studies of these VLC-PUFA.publishedVersio
Investigation of the Functions of n-3 Very-Long-Chain Polyunsaturated Fatty Acids in Skin using in vivo Atlantic Salmon and in vitro Human and Fish Skin Models
No full textpublishedVersio
Changes in the lipid spectra in response to dietary LC <i>n</i>-3 PUFA in selected tissues of mice in the ‘prevention study’.
No full text<p>Mice were fed for 9 weeks the cHF (black triangles), cHF+ω3TG (red circles), or cHF+ω3PL (blue circles) diet, while the last two diets were supplemented with 30 g DHA/EPA per kg. In total, 59, 71 and 61 lipid species were quantified in the liver, epididymal WAT and skeletal muscle, respectively, using time-of-flight secondary ion mass spectrometry (<b>TOF-SIMS</b>) analysis (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038834#pone.0038834.s011" target="_blank">Table S8</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038834#pone.0038834.s012" target="_blank">S9</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038834#pone.0038834.s013" target="_blank">S10</a>). Means±SEM of 3–6 TOF-SIMS spectra from 3 animals per each group were used for orthogonal partial least squares-discriminant analysis (<b>oPLS-DA</b>). Score plots of the liver (<b>A</b>), WAT (<b>B</b>) and skeletal muscle (<b>C</b>) and corresponding variable important to projection (VIP) plots for the first latent variable (<b>D, E, F</b>), respectively. Only variables with VIP scores greater than 1 (denoted by a dashed horizontal line; <b>D-F</b>) and narrow confidence intervals were used for further evaluations, and only those discriminating between cHF+ω3TG and cHF+ω3PL diets (gray bars, <b>D-F</b>) were plotted (G; cHF diet, black bars; cHF+ω3TG diet, red bars; cHF+ω3PL diet; blue bars). See also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038834#pone.0038834.s003" target="_blank">Fig. S3</a> for additional lipid species identified. DAG, diacylglycerol. *Significantly different from cHF (all analyses by ANOVA).</p
Modulation of adipose tissue levels of endocannabinoids and endocannabinoid-like molecules by dietary LC <i>n</i>-3 PUFA in the ‘reversal study’.
No full text<p>Following a 4-month-period of cHF-feeding, mice were fed for additional 9 weeks cHF diet, or treated using either cHF+ω3TG or cHF+ω3PL diet supplemented with 30 g DHA/EPA per kg; all diets also contained 2 g metformin per kg. The effects of LC <i>n</i>-3 PUFA supplementation on adipose tissue levels of 2-arachidonoylglycerol (<b>2-AG</b>) and anandamide (<b>AEA; A</b>), as well as on the levels of <i>N</i>-eicosapentaenoylethanolamine (<b>EPEA</b>) and <i>N</i>-docosahexaenoylethanolamine (<b>DHEA; B</b>); cHF, black bars; cHF+ω3TG, red bars; cHF+ω3PL, blue bars. The relationship between adipocyte size and adipose tissue levels of either 2-AG (<b>C</b>) or DHEA (<b>D</b>) in mice fed cHF (black triangles), cHF+ω3TG (red circles), or cHF+ω3PL (blue circles) diet. Data are means±SEM (<i>n</i> = 8–9). *Significantly different from cHF (t-test or ANOVA); <sup>†</sup>significantly different from cHF+ω3TG (ANOVA).</p
