ABSTRACT
Alzheimer's disease (AD) is characterized by cognitive impairment. It is common in the elderly. Etiologically, dysfunction of cholinergic neurotransmitter system is prominent in AD. However, disease modifying drug for AD is still unavailable. We hypothesized that krill oil and modified krill oil containing 20 % lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA, LPC20K) could play a crucial role in AD by improving cognitive functions measured by several behavioral tests. We found that LPC20K could ameliorate short-term, long-term, spatial, and object recognition memory under cholinergic hypofunction states. To find the underlying mechanism involved in the effect of LPC20K on cognitive function, we investigated changes of signaling molecules using Western blotting. Expression levels of protein kinase C zeta (PKCζ) and postsynaptic density protein 95 (PSD-95), and phosphorylation levels of extracellular signal-regulated kinase (ERK), Ca2+/calmodulin-dependent protein kinase ⠡ (CaMK⠡), and cAMP response element-binding protein (CREB) were significantly increased in LPC20K-administered group compared to those in the memory impairment group. Moreover, the expression levels of BDNF were temporally increased especially 6 or 9 h after administration of LPC20K compared with the control group. These results suggest that LPC20K could ameliorate memory impairment caused by hypocholinergic state by enhancing the expression levels of PKCζ and PSD-95, and phosphorylation levels of ERK, CaMK⠡ and CREB and increasing BDNF expression levels. Therefore, LPC20K could be used as a dietary supplement against cognitive impairment observed in diseases such as AD with a hypocholinergic state.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Euphausiacea , Humans , Animals , Aged , Scopolamine/pharmacology , Euphausiacea/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Maze Learning , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Memory Disorders/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Cholinergic Agents/pharmacology , Hippocampus/metabolism , Cyclic AMP Response Element-Binding Protein/metabolismABSTRACT
Supplementation with marine-derived n-3 long-chain polyunsaturated fatty acids (LC PUFAs), eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) is linked to beneficial health effects in both humans and horses. Krill oil (KO), which is extracted from the Antarctic krill (Euphausia superba), is well documented as a safe and biologically available dietary supplement in humans and several animal species, but there is a lack of documentation regarding its effect as a dietary ingredient for horses. The objective of this study was to test whether KO as a dietary supplement had the ability to raise horse red blood cell (RBC) membrane EPA and DHA, expressed as the n-3 index. Five nonworking Norwegian cold-blooded trotter horse geldings (body weight [BW]: 567 ± 38 kg) were supplemented with KO (10 mL/100 kg BW) for 35 days in a longitudinal study. Blood samples were analysed for RBC membrane fatty acid (FA) profile, haematology and serum biochemistry every 7th day. KO was well accepted by all horses, and no adverse health effects were observed during the 35-day trial period. KO supplementation affected the RBC membrane FA profile by increasing the n-3 index from Day 0 to 35 (Day 0: 0.53% vs. Day 35: 4.05% of total RBC FAs). The observed increase in the sum of EPA and DHA (p < 0.001), total n-3 FAs (p < 0.001) and the reduction of n-6 FAs (p < 0.044) resulted in a lower n-6:n-3 ratio (p < 0.001) by Day 35 of KO supplementation. In conclusion, the RBC n-3 index was increased and the general n-6:n-3 ratio was decreased in horses receiving 35-day dietary KO supplementation.
Subject(s)
Euphausiacea , Fatty Acids, Omega-3 , Animals , Male , Cell Membrane , Dietary Supplements , Docosahexaenoic Acids/pharmacology , Eicosapentaenoic Acid , Euphausiacea/chemistry , Euphausiacea/metabolism , Fatty Acids , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/metabolism , Fish Oils , Horses , Longitudinal StudiesABSTRACT
Osteoporosis, a chronic disease that affects over 200 million people worldwide, presents a substantial medical and socioeconomic burden on the modern society. However, long-term intake of diets supplemented with different polyunsaturated fatty acids (PUFAs) can affect bone metabolism; thus, this study investigated the comparative effects of Antarctic krill oil (AKO, containing n-3 PUFAs) and arachidonic acid-rich oil (AAO, containing n-6 PUFAs) on bone resorption in a mice model of postmenopausal osteoporosis. Mice were orally administered with AKO (200 mg kg-1) or AAO (220 mg kg-1) once daily for 30 days, ovariectomized, followed by the continued administration of the respective samples for 90 days. Biomechanical and histomorphometric analyses revealed that AKO increased the bone mineral density (BMD) to enhance the biomechanical properties by increasing the mineral apposition rate and repairing the microstructure of the trabecular bone, whereas AAO had the opposite effect. The fatty acid analysis of the vertebra showed that AKO increased the n-3 PUFA (especially for DHA) content, thereby decreasing the ratio of n-6/n-3 PUFAs, which was negatively correlated with the BMD. However, AAO had the opposite effect due to high amounts of arachidonic acid. To explore the underlying mechanism responsible for these observations, we compared the classical bone resorption OPG/RANKL/NF-κB pathway mediated by PGE2/EP4. The ratio of n-6/n-3 PUFAs in the bone affected the production of PGE2, a factor regulating the OPG/RANKL pathway, thereby regulating osteoclastogenesis by stimulating the NF-κB pathway. The results of ELISA, qRT-PCR, and western blot demonstrated that AKO reduced the secretion of PGE2 and the expression of EP4, upregulating the ratio of OPG/RANKL in the bone, thereby decreasing TRAF6 expression to inhibit the activation of the NF-κB signaling pathway, and finally inhibiting the expression of nuclear transcription factors (c-fos and NFATc1) to prevent excessive osteoclastogenesis (TRACP, MMP-9, and Cath-K). Arachidonic acid is a precursor of PGE2 synthesis. AAO showed the opposite trend through the same pathway. Thus, AKO could significantly improve osteoporosis via the OPG/RANKL/NF-κB pathway mediated by PGE2/EP4 to inhibit osteoclastogenesis, whereas AAO aggravated osteoporosis via the same pathway. This is the first study to systematically compare the effects and mechanism of AKO and AAO in regulating bone resorption in osteoporotic mice to support recommendations on fatty acid types in dietary oils for an osteoporotic population.
Subject(s)
Arachidonic Acid/pharmacology , Bone Resorption/drug therapy , Euphausiacea/metabolism , Oils/pharmacology , Animals , Bone Density/drug effects , Bone and Bones/metabolism , Disease Models, Animal , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-6/pharmacology , Female , Humans , Matrix Metalloproteinase 9 , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Osteoporosis, Postmenopausal/drug therapy , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Signal Transduction/drug effects , TNF Receptor-Associated Factor 6/metabolism , Tartrate-Resistant Acid PhosphataseABSTRACT
BACKGROUND AND OBJECTIVES: Krill oil (KO) and fish oil (FO) are good sources of health-benefiting long chain n- 3 polyunsaturated fatty acids (LC n-3 PUFA), EPA and DHA. There are conflicting outcomes on the bioavailability of LC n-3 PUFA from KO compared with FO. This study investigated the postprandial incorporation of LC n- 3 PUFA into plasma lipids following consumption of 5 capsules of KO or FO in comparison with olive oil (OO) control in healthy women. METHODS AND STUDY DESIGN: 10 women (aged 18-45 years) consumed a high-fat (15 g) breakfast, supplemented with 5 g of KO, FO, or OO in a random order with a minimum seven-day washout period between the supplementations. The LC n-3 PUFA content in KO was 907 mg compared with 1441 mg in FO. Blood samples were collected in the fasting state and for the next 5 hours after test meal consumption on an hourly basis. RESULTS: Significant increases in plasma EPA concentrations were observed starting at 2 h after KO and FO consumption (p<0.05). There were no significant changes in either DHA or DPA between the three groups. The increases in plasma EPA concentrations were similar between the KO and FO groups (p>0.05). CONCLUSIONS: The lower dose (31%) of EPA from KO led to a similar plasma EPA concentration as in the FO group, suggesting that EPA from KO may be more efficiently incorporated into plasma. This may be related to the high content of phospholipids and free fatty acids in KO.
Subject(s)
Euphausiacea/metabolism , Fatty Acids, Omega-3/blood , Fish Oils/administration & dosage , Fish Oils/blood , Postprandial Period , Adolescent , Adult , Animals , Cross-Over Studies , Female , Humans , Middle Aged , Oils/administration & dosage , Oils/metabolism , Reference Values , Shellfish , Young AdultABSTRACT
The effects of dietary krill oil on neurocognitive functions and proteomic changes in brain tissues of d-galactose-induced aging mice were evaluated. Dietary krill oil enhanced the neurocognitive functions of aging mice with a significant (P < 0.05) decrease in escape latency and an increase in the number of times of crossing over the hidden platform during the Morris water maze test. Krill oil was also found to protect against oxidative damage, lipid peroxidation and neurodegenerative diseases. Oxidative stress biomarkers of aging mice administered with krill oil showed significant (P < 0.05) improvement with an increase in serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels; there were insignificant changes in the serum malondialdehyde (MDA) level. In terms of proteomic changes, krill oil resulted in upregulation of the Celsr3 and Ppp1r1b gene expression, which contribute to brain development, learning and memory behavior processes. In particular, the Ppp1r1b gene is associated with the inhibition of dopamine releases, which decreases the motivation for learning.
Subject(s)
Aging/metabolism , Brain/metabolism , Dietary Fats, Unsaturated/metabolism , Euphausiacea/metabolism , Galactose/adverse effects , Plant Oils/metabolism , Aging/psychology , Animals , Cognition , Euphausiacea/chemistry , Glutathione Peroxidase/blood , Humans , Male , Malondialdehyde/metabolism , Memory , Mice , Proteomics , Superoxide Dismutase/bloodABSTRACT
The availability of micronutrients is a key factor that affects primary productivity in High Nutrient Low Chlorophyll (HNLC) regions of the Southern Ocean. Nutrient supply is governed by a range of physical, chemical and biological processes, and there are significant feedbacks within the ecosystem. It has been suggested that baleen whales form a crucial part of biogeochemical cycling processes through the consumption of nutrient-rich krill and subsequent defecation, but data on their contribution are scarce. We analysed the concentration of iron, cadmium, manganese, cobalt, copper, zinc, phosphorus and carbon in baleen whale faeces and muscle, and krill tissue using inductively coupled plasma mass spectrometry. Metal concentrations in krill tissue were between 20 thousand and 4.8 million times higher than typical Southern Ocean HNLC seawater concentrations, while whale faecal matter was between 276 thousand and 10 million times higher. These findings suggest that krill act as a mechanism for concentrating and retaining elements in the surface layer, which are subsequently released back into the ocean, once eaten by whales, through defecation. Trace metal to carbon ratios were also higher in whale faeces compared to whale muscle indicating that whales are concentrating carbon and actively defecating trace elements. Consequently, recovery of the great whales may facilitate the recycling of nutrients via defecation, which may affect productivity in HNLC areas.
Subject(s)
Ecosystem , Euphausiacea/metabolism , Micronutrients/metabolism , Whales/metabolism , Animals , Carbon/analysis , Carbon/metabolism , Feces/chemistry , Mass Spectrometry/methods , Metals/analysis , Metals/metabolism , Micronutrients/analysis , Muscles/chemistry , Phosphorus/analysis , Phosphorus/metabolism , Seawater/chemistry , Trace Elements/analysis , Trace Elements/metabolismABSTRACT
Omega-3 fatty acids eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA), provide significant health benefits for brain function/development and cardiovascular conditions. However, most EPA and DHA for human consumption is sourced from small fatty fish caught in coastal waters and, with depleting global fish stocks, recent research has been directed towards more sustainable sources. These include aquaculture with plant-based feeds, krill, marine microalgae, microalgae-like protists and genetically-modified plants. To meet the increasing demand for EPA and DHA, further developments are needed towards land-based sources. In particular large-scale cultivation of microalgae and plants is likely to become a reality with expected reductions in production costs, yield increasese and the adequate addressing of genetically modified food acceptance issues.
Subject(s)
Conservation of Natural Resources/methods , Fatty Acids, Omega-3/supply & distribution , Animals , Aquaculture/statistics & numerical data , Dietary Supplements/supply & distribution , Docosahexaenoic Acids/biosynthesis , Docosahexaenoic Acids/supply & distribution , Eicosapentaenoic Acid/biosynthesis , Eicosapentaenoic Acid/supply & distribution , Euphausiacea/metabolism , Fatty Acids, Omega-3/biosynthesis , Functional Food/supply & distribution , Humans , Microalgae/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolismABSTRACT
High performance liquid chromatography-electrospray tandem mass spectrometry was used to elucidate the phospholipids in krill oil extracted from Euphausia superba, an emerging source for human nutritional supplements. The study was carried out in order to map the species of the choline-containing phospholipid classes: phosphatidylcholine and lyso-phosphatidylcholine. In addition, the prevalent phosphatidylcholine class was quantified and the results compared with prior analysis. The qualification was performed with separation on a reverse phase chromatography column, while the quantification was obtained with class separation on a normal phase chromatography column. An Orbitrap system was used for the detection, and pulsed-Q dissociation fragmentation was utilized for the identification of the species. An asymmetrical exclusion list was applied for detection of phospholipid species of lower concentration, significantly improving the number of species observed. A total of 69 choline-containing phospholipids were detected, whereof 60 phosphatidylcholine substances, among others seven with probable omega-3 fatty acids in both sn-1 and sn-2. The phosphatidylcholine concentration was estimated to be 34 ± 5 g/100 g oil (n = 5). These results confirm the complexity of the phospholipid composition of krill oil, and the presence of long chained, heavily unsaturated fatty acids.
Subject(s)
Euphausiacea/chemistry , Euphausiacea/metabolism , Phosphatidylcholines/chemistry , Animals , Chromatography, High Pressure Liquid , Chromatography, Reverse-Phase , Fatty Acids, Omega-3/chemistry , Oils/chemistry , Phosphatidylcholines/analysis , Tandem Mass SpectrometryABSTRACT
Female Sprague-Dawley rats provide an animal model for studying the role of nutrition in renal health due to their sensitivity to diet-induced alterations in kidney function. Nephrocalcinosis, a common renal abnormality found in rats, has been implicated in subsequent renal failure. Simple dietary manipulations, such as changing the source of dietary protein, may influence nephrocalcinosis. This study evaluates the consumption of krill protein concentrate (KPC), a novel and high-quality protein, on renal and bone health. Young female Sprague-Dawley rats (n = 10/group) were individually housed in metabolic cages and fed ad libitum diets consisting of 10% crude protein supplied as KPC or casein for 4 weeks. Diets were isocaloric, isonitrogenous, and matched for calcium (Ca) and phosphorus (P). Urinary n-acetyl glucosaminidase (NAG) was measured and kidney histology performed to assess kidney damage. Biomarkers of kidney function were determined by calorimetric assays. Ca and P balance and bone concentrations were measured using inductively coupled plasma mass spectrometry. Femoral strength was determined by three-point bend testing. Rats fed KPC had lower (P = 0.005) urinary NAG levels and minimal microtubular Ca deposition compared to rats fed casein. There was a tendency (P < 0.06) for higher glomerular filtration rates and lower proteinuria, and higher (P = 0.03) urinary output in rats fed KPC compared to casein. There were no differences in Ca and P balance or bone measurements of total bone mineral content, Ca, P or strength between rats fed KPC and casein. Based on the study results, KPC prevented early renal injury leading to nephrocalcinosis and potential bone loss.