P839 - THE OMEGA-3 TRANSPORTER, MFSD2A, IS MODULATED IN THE HYPOTHALAMIC BLOOD-BRAIN BARRIER BY DIET-INDUCED OBESITY AND AGE ADVANCING

P839

THE OMEGA-3 TRANSPORTER, MFSD2A, IS MODULATED IN THE HYPOTHALAMIC BLOOD-BRAIN BARRIER BY DIET-INDUCED OBESITY AND AGE ADVANCING

C. V. A. Cunha¹, L. K. Oharomari¹, J. B. Lima¹, L. M. Paula¹, C. K. Katashima², T. S. Rios¹, T. Meneguelli¹, A. P. Pinto³, D. H. T. Buoro¹, F. D. S. Carneiro², E. R. Ropelle², J. R. Pauli², A. S. R. Silva³, A. M. Lottenberg^4,5,*, D. E. Cintra^1,4

¹Laboratory of Nutritional Genomics, University of Campinas (UNICAMP), ²Laboratory of Molecular Biology of Exercise, University of Campinas (UNICAMP), Limeira, ³School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), , Ribeirão Preto, ⁴Nutritional Genomics and Lipids Research Center (CELN), Limeira, ⁵Hospital Israelita Albert Einstein, São Paulo, Brazil

Rationale: MFSD2a is the primary transporter of omega-3 (ω3) polyunsaturated fatty acid from the blood to the central nervous system and contributes to the maintenance of blood-brain barrier (BBB) permeability, a structure that is disrupted in obesity under systemic low-grade inflammation. However, little is known regarding how diet-induced obesity influences hypothalamic MFSD2a content.

Methods: Male Swiss mice were utilized to evaluate whether 8/12 weeks of a high-fat diet (HF) inducing obesity, 5 days of ω3 source oil intake, central administration of inflammatory cytokine or saturated fatty acid, and different times of exposure to HF can modify hypothalamic MFSD2a content.

Results: Obese animals exhibit a higher MFSD2a content than the control group, without different gene expression. MFSD2a was observed with immunofluorescence analyses in four different hypothalamic areas, with the paraventricular nucleus and arcuate nucleus showing more MFSD2a coverage in obese animals. MFSD2a content or the hypothalamic fatty acids profile has no changes after five days of ω3-rich oil intake. However, changes in the lipid profile were observed in the serum. Intracerebroventricular administration of TNFα or palmitic acid did not alter the hypothalamic MFSD2a content. Nonetheless, the time of exposure to the HF diet and the increasing age can modulate the hypothalamic content of MFsd2a. 

Conclusion:  Our study demonstrated that the leading omega-3 transporter in the hypothalamus is nutritionally and physiologically altered, opening the door to new therapies that target lipid transport in the central nervous system. Grant: FAPESP 2019-13210-0; 2023-12208-7

Disclosure of Interest: None declared