The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice

Macura, Irena Jovanović; Djuričić, Ivana; Major, Tamara; Milanović, Desanka; Brkic, Marjana; Šobajić, Sladjana; Kanazir, Selma; Ivković, Sanja

doi:10.1016/j.jff.2022.105302

Cited by 2 publications

(9 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another function of Srebp1-c is to enhance the transcription of genes regulating fatty acid synthesis ( 60 ). However, contrary to the reported decrease in Srebf1 in adult animals supplemented with FO associated with the increase in Mfsd2a ( 54 ), the expression levels of Srebf1 remained unchanged in the retinas ( Figure 3C ) and increased in the RPE of FO-supplemented offspring (6.5-fold increase, Figure 3C ).…”

Section: Resultscontrasting

confidence: 83%

“…The protective role of RPE in maintaining retinal homeostasis could be one of the reasons for these changes, although other mechanisms cannot be ruled out. In a previous study, we demonstrated that high-dose fish oil (FO) supplementation maintained for 3 weeks in 3-month-old mice (adulthood) significantly altered n-3 PUFAs in the retinas and RPE but that the levels of DHA were also unaltered ( 54 ). These results confirm that the rigorous regulation of DHA homeostasis in the retina is necessary for the proper functioning of photoreceptors, regardless of the age of the supplementation.…”

Section: Discussionmentioning

confidence: 99%

“…Increased Mfsd2a levels in the retina may contribute to DHA homeostasis, maintaining lipid saturation and cell membrane fluidity ( 48 ). In addition, the increase in the expression of the DHA transporter, Mfsd2a , was observed both in the adult supplementation and in the offspring that was supplemented during development ( 54 ) suggesting that FO supplementation is responsible for this increase, although it is possible that the mechanisms involved in the upregulation of Mfsd2a differ depending on the time of the supplementation.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, we demonstrated that high-dose fish oil (FO) supplementation during adulthood led to significant alterations in lipid content and the increased expression of genes governing DHA transport (Mfsd2a) and cholesterol homeostasis in the retina and retinal pigmented epithelium (RPE) ( 54 ). However, the enduring effects on the retinas and RPE in the offspring resulting from high-dose FO supplementation during pregnancy and lactation remain unknown.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring

Macura,

Djuricic,

Major

et al. 2024

Front. Nutr.

Self Cite

View full text Add to dashboard Cite

IntroductionDuring fetal development, the proper development of neural and visual systems relies on the maternal supplementation of omega-3 fatty acids through placental transfer. Pregnant women are strongly advised to augment their diet with additional sources of omega-3, such as fish oil (FO). This supplementation has been linked to a reduced risk of preterm birth, pre-eclampsia, and perinatal depression. Recently, higher doses of omega-3 supplementation have been recommended for pregnant women. Considering that omega-3 fatty acids, particularly docosahexaenoic acid (DHA), play a crucial role in maintaining the delicate homeostasis required for the proper functioning of the retina and photoreceptors the effects of high-dose fish oil (FO) supplementation during pregnancy and lactation on the retina and retinal pigmented epithelium (RPE) in healthy offspring warrant better understanding.MethodsThe fatty acid content and the changes in the expression of the genes regulating cholesterol homeostasis and DHA transport in the retina and RPE were evaluated following the high-dose FO supplementation.ResultsOur study demonstrated that despite the high-dose FO treatment during pregnancy and lactation, the rigorous DHA homeostasis in the retina and RPE of the two-month-old offspring remained balanced. Another significant finding of this study is the increase in the expression levels of major facilitator superfamily domain-containing protein (Mfsd2a), a primary DHA transporter. Mfsd2a also serves as a major regulator of transcytosis during development, and a reduction in Mfsd2a levels poses a major risk for the development of leaky blood vessels.ConclusionImpairment of the blood-retinal barrier (BRB) is associated with the development of numerous ocular diseases, and a better understanding of how to manipulate transcytosis in the BRB during development can enhance drug delivery through the BRB or contribute to the repair of central nervous system (CNS) barriers.

show abstract

Section: Resultscontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring

Macura,

Djuricic,

Major

et al. 2024

Front. Nutr.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent research confirmed that storax attenuated BBB disruption by upregulating Mfsd2a and inhibiting Cav-1 in the endothelial cells in order to arrest the progression of cerebral ischemia [ 67 ]. Similarly, treatment with LPC-DHA, transported through Mfsd2a, strongly improved retinal function in 5xFAD mice [ 68 ], and treatment with fish oil significantly increased Mfsd2a expression and blood vessel coverage in the retinas of wild-type mice [ 69 ]. Finally, the overexpression of Mfsd2a in the eye was reported to decrease retinal neovascularization and vascular leakage in mouse models of retinopathy and, importantly, co-treatment with DHA had a synergistic positive effect [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease

Jovanovic Macura,

Zivanovic,

Perovic

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) accumulation in the blood vessels and is associated with cognitive impairment in Alzheimer’s disease (AD). The increased accumulation of Aβ is also present in the retinal blood vessels and a significant correlation between retinal and brain amyloid deposition was demonstrated in living patients and animal AD models. The Aβ accumulation in the retinal blood vessels can be the result of impaired transcytosis and/or the dysfunctional ocular glymphatic system in AD and during aging. We analyzed the changes in the mRNA and protein expression of major facilitator superfamily domain-containing protein2a (Mfsd2a), the major regulator of transcytosis, and of Aquaporin4 (Aqp4), the key player implicated in the functioning of the glymphatic system, in the retinas of 4- and 12-month-old WT and 5xFAD female mice. A strong decrease in the Mfsd2a mRNA and protein expression was observed in the 4 M and 12 M 5xFAD and 12 M WT retinas. The increase in the expression of srebp1-c could be at least partially responsible for the Mfsd2a decrease in the 4 M 5xFAD retinas. The decrease in the pericyte (CD13+) coverage of retinal blood vessels in the 4 M and 12 M 5xFAD retinas and in the 12 M WT retinas suggests that pericyte loss could be associated with the Mfsd2a downregulation in these experimental groups. The observed increase in Aqp4 expression in 4 M and 12 M 5xFAD and 12 M WT retinas accompanied by the decreased perivascular Aqp4 expression is indicative of the impaired glymphatic system. The findings in this study reveal the impaired Mfsd2a and Aqp4 expression and Aqp4 perivascular mislocalization in retinal blood vessels during physiological (WT) and pathological (5xFAD) aging, indicating their importance as putative targets for the development of new treatments that can improve the regulation of transcytosis or the function of the glymphatic system.

show abstract

The high-dose fish oil supplementation increased Mfsd2a expression without altering DHA levels in the retina of healthy mice

Cited by 2 publications

References 64 publications

The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring

The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring

The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer’s Disease

Contact Info

Product

Resources

About