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bioRxiv · 10.1101/2023.06.01.543121

Adult-onset CNS sulfatide deficiency causes sex-dependent metabolic disruption in aging

Qiu, S.·He, S.·Wang, J.·Wang, H.·Bhattacharjee, A.·Li, X.·Saeed, M.·Dupree, J. L.·Han, X.
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Abstract

The interconnection between obesity and central nervous system (CNS) neurological dysfunction has been widely appreciated. Accumulating evidence demonstrates that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. However, the extent to which CNS disruption influences peripheral metabolism remains to be elucidated. We previously reported that myelin-enriched sulfatide loss leads to CNS neuroinflammation and cognitive decline. In this study, we further investigated the impact of CNS sulfatide deficiency on peripheral metabolism while considering sex- and age-specific effects. We found that female sulfatide-deficient mice gained significantly more body weight, exhibited higher basal glucose levels, and were glucose intolerant during glucose-tolerance test (GTT) compared to age-matched controls under a normal diet, whereas male sulfatide-deficient mice only displayed glucose intolerance at a much older age compared to female sulfatide-deficient mice. Mechanistically, we found the increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypo-thalamus, in a sex-specific manner. Our results suggest that CNS sulfatide deficiency leads to sex-specific alterations in energy homeostasis via dysregulated hypothalamic control of food-intake.

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Qiu, S., He, S., Wang, J., Wang, H., Bhattacharjee, A., Li, X., Saeed, M., Dupree, J. L., Han, X.. 2023-06-03. Adult-onset CNS sulfatide deficiency causes sex-dependent metabolic disruption in aging. https://doi.org/10.1101/2023.06.01.543121

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