FMRP-absence-induced up-regulation of hypothalamic MAP1B expression decreases AgRP level linking with reduces in food intake and body weight
| Autor: | Fei Hu, Wei-Wen Sun, Jing-Yi Long, Wei Jiang, Hai-Bin Xia, Jun-Yi Fu, Yong-Hong Yi, Mei-Mei Gao, Yue-Sheng Long, Ping Lu, Wen-Cai Feng |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine congenital hereditary and neonatal diseases and abnormalities Hypothalamus Gene Expression RNA-binding protein Eating Fragile X Mental Retardation Protein Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation Arcuate nucleus Gene expression medicine Animals Agouti-Related Protein Mice Knockout Gene knockdown Arc (protein) Chemistry Body Weight digestive oral and skin physiology Cell Biology medicine.disease Up-Regulation nervous system diseases Cell biology Fragile X syndrome 030104 developmental biology nervous system Microtubule-Associated Proteins hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery |
| Zdroj: | Neurochemistry International. 140:104847 |
| ISSN: | 0197-0186 |
| Popis: | Fragile X mental retardation protein (FMRP), strongly associated with fragile X syndrome, plays important roles by regulating gene expression via interacting with other RNA binding proteins in the brain. However, the role of FMRP in hypothalamus, a central part responsible for metabolic control, is poorly known. Our study shows that FMRP is primarily located in the hypothalamic arcuate nucleus (ARC). Using proteomic analysis, we identified 56 up-regulated and 22 down-regulated proteins in the hypothalamus of Map1b KO mice, with microtubule-associated protein 1 B (MAP1B) being the most outstanding increased protein (more than 10 folds). Immunofluorescent assays showed that MAP1B significantly increased in the Map1b-KO ARC, in which the number of agouti-related peptide (AgRP)-staining neurons significantly reduced, but not altered for pro-opiomelanocortin (POMC) neurons. We further showed an age-dependent reduces in food intake and body weight of the KO mice, along with the decreases of MAP1B and AgRP at the same time points. In hypothalamic GT1-7 cells, the AgRP expression decreased upon knockdown of FMRP or overexpression of MAP1B, and increased in response to overexpression of FMRP or knockdown of MAP1B. Co-knockdown or co-overexpression of FMRP and MAP1B led to a reverse expression of AgRP compared to overexpression of knockdown of FMRP alone, demonstrating that MAP1B is essential for the regulatory effect of FMRP on AgRP expression. Taken together, these data suggest that FMRP-deficiency-induced increase of hypothalamic MAP1B and decrease of AgRP might be associated with reduces in food intake and body weight. |
| Databáze: | OpenAIRE |
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