The influence of aerobic exercise in the content of the MFSD2A transporter in brain areas

Abstract

Background

Obesity is associated with chronic inflammation, neuroinflammation, and impairment of the blood-brain-barrier (BBB), contributing to neural dysfunctions and metabolic dysregulation in the hypothalamus and hippocampus. MFSD2A is a lipid transporter expressed in the cerebral endothelium, essential in BBB integrity and in the transport of omega-3 fatty acids, particularly DHA, into the central nervous system. Since exercise exerts anti-inflammatory and neuroprotective effects, this study evaluates the ability of chronic aerobic exercise to modulate MFSD2A protein content in the hypothalamus and hippocampus of obese mice.

Obesity is associated with chronic inflammation, neuroinflammation, and impairment of the blood-brain-barrier (BBB), contributing to neural dysfunctions and metabolic dysregulation in the hypothalamus and hippocampus. MFSD2A is a lipid transporter expressed in the cerebral endothelium, essential in BBB integrity and in the transport of omega-3 fatty acids, particularly DHA, into the central nervous system. Since exercise exerts anti-inflammatory and neuroprotective effects, this study evaluates the ability of chronic aerobic exercise to modulate MFSD2A protein content in the hypothalamus and hippocampus of obese mice.

Objective

Measure the impact of exercise in the MFSD2a content in the hypothalamus and hippocampus areas.

Measure the impact of exercise in the MFSD2a content in the hypothalamus and hippocampus areas.

Methods

Male Swiss mice (ethical acceptance: CEUA 6230-1/2023) were randomly allocated into the experimental groups (high fat [HF] and high fat + exercise [HF + EXE]). Obesity was induced by a high-fat diet consumed for eight weeks, while the control group (CT) animals received a standard diet. After obesity establishment, mice remained sedentary or went through a chronic aerobic exercise protocol on a treadmill for four weeks. Body weight, food intake, glycemia, insulin and glucose sensitivity were monitored throughout the experimental period. After 24 h of the last exercise session, hypothalamic and hippocampal samples were collected for molecular analyses. MFSD2A protein content was quantified by Western blotting, and its distribution through hypothalamic regions associated with the BBB was evaluated through immunofluorescence. Statistical analyses were performed using ANOVA followed by Bonferroni post hoc tests (P < 0.05).

Male Swiss mice (ethical acceptance: CEUA 6230-1/2023) were randomly allocated into the experimental groups (high fat [HF] and high fat + exercise [HF + EXE]). Obesity was induced by a high-fat diet consumed for eight weeks, while the control group (CT) animals received a standard diet. After obesity establishment, mice remained sedentary or went through a chronic aerobic exercise protocol on a treadmill for four weeks. Body weight, food intake, glycemia, insulin and glucose sensitivity were monitored throughout the experimental period. After 24 h of the last exercise session, hypothalamic and hippocampal samples were collected for molecular analyses. MFSD2A protein content was quantified by Western blotting, and its distribution through hypothalamic regions associated with the BBB was evaluated through immunofluorescence. Statistical analyses were performed using ANOVA followed by Bonferroni post hoc tests (P < 0.05).

Results

Chronic aerobic exercise significantly increased MFSD2A protein content in the hippocampus of HF + EXE compared to HF mice (P = 0.002), but not in the hypothalamus (P = 0.0564). Immunofluorescence of the hypothalamus areas revealed significant changes in the MFSD2A-positive area among groups in the paraventricular nucleus (P = 0.0296). The same analysis will be performed on the hippocampus area.

Chronic aerobic exercise significantly increased MFSD2A protein content in the hippocampus of HF + EXE compared to HF mice (P = 0.002), but not in the hypothalamus (P = 0.0564). Immunofluorescence of the hypothalamus areas revealed significant changes in the MFSD2A-positive area among groups in the paraventricular nucleus (P = 0.0296). The same analysis will be performed on the hippocampus area.

Conclusion

Chronic aerobic exercise upregulated hippocampus MFSD2A protein in obese mice and the same was observed in the hypothalamus, specifically in the paraventricular nucleus, a key region for energy homeostasis and autonomic regulation. Together, these findings suggest that exercise may positively modulate BBB integrity and omega-3 fatty acid transport mechanisms within metabolically relevant hypothalamic regions, reinforcing its potential as a neuroprotective strategy under obesogenic conditions.

Chronic aerobic exercise upregulated hippocampus MFSD2A protein in obese mice and the same was observed in the hypothalamus, specifically in the paraventricular nucleus, a key region for energy homeostasis and autonomic regulation. Together, these findings suggest that exercise may positively modulate BBB integrity and omega-3 fatty acid transport mechanisms within metabolically relevant hypothalamic regions, reinforcing its potential as a neuroprotective strategy under obesogenic conditions.