The influence of diet, age, and obesity on hypothalamic omega-3 fatty acid transporter MFSD2a

Inflammatory proteins present in the context of obesity influence the general permeability of organic biological barriers, including the blood-brain barrier (BBB). Inflammation alters junction proteins, resulting in increased permeability, and may also influence the response pattern of barrier proteins responsible for intracellular nutrient transport. Focusing on the MFSD2a protein (major facilitator superfamily domain containing 2 A), which is present in the BBB, is an important translocator of omega-3 fatty acid (ω3) from the periphery to the central nervous system (CNS), this study aimed to assess the impact of obesity induced by a high-fat diet (HF) on the MFSD2a modulation in the hypothalamus of mice. Male Swiss mice were subjected to HF, and after the onset of obesity, the MFSD2a gene expression, protein content, and their distribution through the hypothalamic areas were measured. Also, obese animals were treated with ω3-rich oil orally to measure the ω3 translocation to the brain. Palmitate or TNFα was administered intracerebroventricularly (i.c.v) to test the mechanism enrolled on MFSD2a modulation. Surprisingly, MFSD2a was increased in the hypothalamic MFSD2a induced by HF consumption. The biomolecular mapping showed wide MFSD2a distribution throughout the different hypothalamic nuclei but increased in arcuate and paraventricular nucleus induced by HF-diet. The ω3 translocator is modulated over the animal's lifetime under both CT and HF diets. The i.c.v. administration of TNFα or palmitic did not alter the translocator, thus, the mechanistic influence of obesity on MFSD2a is still open. The supply of ω3-rich oils to obese mice had no impact on their central bioaccessibility. These nutrigenomic approaches revealed that not only the obesogenic process impacts the MFSD2a protein in the hypothalamus but also environmental and life circumstances.