Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging
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 perip...
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10483 |
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| author | Shulan Qiu Sijia He Jianing Wang Hu Wang Anindita Bhattacharjee Xin Li Moawiz Saeed Jeffrey L. Dupree Xianlin Han |
| author_facet | Shulan Qiu Sijia He Jianing Wang Hu Wang Anindita Bhattacharjee Xin Li Moawiz Saeed Jeffrey L. Dupree Xianlin Han |
| author_sort | Shulan Qiu |
| collection | DOAJ |
| description | 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 that increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypothalamus, 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. |
| first_indexed | 2024-03-11T01:40:26Z |
| format | Article |
| id | doaj.art-d5f6253d88d246d59f08f75eed99eaba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:40:26Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d5f6253d88d246d59f08f75eed99eaba2023-11-18T16:38:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131048310.3390/ijms241310483Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in AgingShulan Qiu0Sijia He1Jianing Wang2Hu Wang3Anindita Bhattacharjee4Xin Li5Moawiz Saeed6Jeffrey L. Dupree7Xianlin Han8Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USABarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USABarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USABarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USABarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USABarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USABarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USADepartment of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23284, USABarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USAThe 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 that increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypothalamus, 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.https://www.mdpi.com/1422-0067/24/13/10483sulfatideglucose metabolismfood intakeAlzheimer’s diseaseaging |
| spellingShingle | Shulan Qiu Sijia He Jianing Wang Hu Wang Anindita Bhattacharjee Xin Li Moawiz Saeed Jeffrey L. Dupree Xianlin Han Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging International Journal of Molecular Sciences sulfatide glucose metabolism food intake Alzheimer’s disease aging |
| title | Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging |
| title_full | Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging |
| title_fullStr | Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging |
| title_full_unstemmed | Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging |
| title_short | Adult-Onset CNS Sulfatide Deficiency Causes Sex-Dependent Metabolic Disruption in Aging |
| title_sort | adult onset cns sulfatide deficiency causes sex dependent metabolic disruption in aging |
| topic | sulfatide glucose metabolism food intake Alzheimer’s disease aging |
| url | https://www.mdpi.com/1422-0067/24/13/10483 |
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