Acute EPA-induced learning and memory impairment in mice is prevented by DHA

Liu, Jihong; Wang, Qian; You, Qiang-Long; Li, Zelin; Hu, Nan; Wang, Yan; Jin, Zeng-Lin; Li, Shu-Ji; Li, Xiaowen; Yang, Jian‐Ming; Zhu, Xinhong; Dai, Yifan; Bai, Xiaochun; Gao, Tianming

doi:10.1038/s41467-020-19255-1

Cited by 52 publications

(23 citation statements)

References 82 publications

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“…Moreover, they can also limit cholesterol uptake, complementary to SREBP mediated effects [29]. Improved cognitive abilities are also confirmed by the significant decrease of EPA plasma concentrations in treated AD mice, in line with a recent study suggesting that this n-3 polyunsaturated fatty acid contributed to impair memory and learning in animal models [65].…”

Section: Discussionsupporting

confidence: 80%

Gut microbiota modulation in Alzheimer's disease: Focus on lipid metabolism

et al. 2022

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Section: Discussionsupporting

confidence: 80%

Gut microbiota modulation in Alzheimer's disease: Focus on lipid metabolism

et al. 2022

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“…Although LT-krill oil results in relatively higher enrichment of brain DHA compared with EPA, EPA is thought to be beneficial for a range of peripheral and brain relevant functions and conditions (e.g., depression, cardiovascular disease). However, acute free (non-LPC) EPA treatment has been reported to impair learning and memory as well as hippocampal function in mice, which is prevented by co-treatment with DHA ( Liu et al, 2020 ). Although these data draw into question the acute benefit of EPA, EPA as free acid is taken up through by diffusion into the brain and is mostly oxidized ( Chen and Bazinet, 2015 ), whereas EPA in the LPC form is transported by a specific transporter (Mfsd2a) and may be beneficial.…”

Section: Discussionmentioning

confidence: 99%

LPC-DHA/EPA-Enriched Diets Increase Brain DHA and Modulate Behavior in Mice That Express Human APOE4

et al. 2021

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Compared with APOE3, APOE4 is associated with greater age-related cognitive decline and higher risk of neurodegenerative disorders. Therefore, development of supplements that target APOE genotype-modulated processes could provide a great benefit for the aging population. Evidence suggests a link between APOE genotype and docosahexaenoic acid (DHA); however, clinical studies with current DHA supplements have produced negative results in dementia. The lack of beneficial effects with current DHA supplements may be related to limited bioavailability, as the optimal form of DHA for brain uptake is lysophosphatidylcholine (LPC)-DHA. We previously developed a method to enrich the LPC-DHA content of krill oil through lipase treatment (LT-krill oil), which resulted in fivefold higher enrichment in brain DHA levels in wild-type mice compared with untreated krill oil. Here, we evaluated the effect of a control diet, diet containing krill oil, or a diet containing LT-krill oil in APOE3- and APOE4-targeted replacement mice (APOE-TR mice; treated from 4 to 12 months of age). We found that DHA levels in the plasma and hippocampus are lower in APOE4-TR mice and that LT-krill oil increased DHA levels in the plasma and hippocampus of both APOE3- and APOE4-TR mice. In APOE4-TR mice, LT-krill oil treatment resulted in higher levels of the synaptic vesicle protein SV2A and improved performance on the novel object recognition test. In conclusion, our data demonstrate that LPC-DHA/EPA-enriched krill oil can increase brain DHA and improve memory-relevant behavior in mice that express APOE4. Therefore, long-term use of LT-krill oil supplements may on some level protect against age-related neurodegeneration.

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“…The plasma levels showed similar results (Figure 4a). Consumption of these omega-3 fatty acids has been reported to exert many beneficial effects on human health, e.g., improved antiinflammatory functions, cognitive functions, and antioxidative effects, as well as reduced lipid accumulation [3,23,24]. We could not obtain the mechanism to explain why the mice consumed the diet containing fish oil at the end of the dark period, but such selective consumption of fish oil might affect excess body weight.…”

Section: Discussionmentioning

confidence: 90%

Selective Consumption of Fish Oil at End of the Day Increases the Physiological Fatty Acid Compositions of Eicosapentaenoic Acid and Docosahexaenoic Acid in Mice

et al. 2022

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Diets with high daily fat consumption are associated with excess weight. However, the effects of fat type and consumption timing on excess weight remain unclear. We investigated the selection of a 30% (w/w) fat diet of soybean oil (SOY), lard (LARD), and fish oil (FISH) on the metabolic parameters of mice. Male C57BL/6 mice were divided into the double SOY-box (w-SOY), SOY-box/LARD-box (SOY-vs-LARD), or SOY-box/FISH-box (SOY-vs-FISH) groups and allowed to selectively consume for 8 weeks. The total energy intake was similar for all groups, but the mice selectively chose to consume LARD over SOY and SOY over FISH. Body weight in the SOY-vs-LARD group was significantly higher than that in the w-SOY and SOY-vs-FISH groups. Additionally, minimal but selective consumption of an omega-3 fatty-acid-rich FISH diet at the end of the active period increased the physiological fatty acid compositions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the SOY-vs-FISH group; their metabolic parameters were also lower than the SOY-vs-LARD group. In conclusion, selectively consuming small amounts of fish oil at the end of the day may prevent excess weight compared with LARD consumption.

show abstract

Acute EPA-induced learning and memory impairment in mice is prevented by DHA

Cited by 52 publications

References 82 publications

Gut microbiota modulation in Alzheimer's disease: Focus on lipid metabolism

Gut microbiota modulation in Alzheimer's disease: Focus on lipid metabolism

LPC-DHA/EPA-Enriched Diets Increase Brain DHA and Modulate Behavior in Mice That Express Human APOE4

Selective Consumption of Fish Oil at End of the Day Increases the Physiological Fatty Acid Compositions of Eicosapentaenoic Acid and Docosahexaenoic Acid in Mice

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