Aging-Induced Brain-Derived Neurotrophic Factor in Adipocyte Progenitors Contributes to Adipose Tissue Dysfunction
| Autor: | Sang Yeop Ahn, Yeonho Son, Young Suk Jung, Hyun Doo Song, Ji Hyun Park, Seun Akindehin, Sang Nam Kim, Yun Hee Lee, Abhirup Saha, Minsu Kim, Yoon Keun Cho |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Senescence medicine.medical_specialty adipocyte progenitors Adipose tissue White adipose tissue Biology Orginal Article Pathology and Forensic Medicine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Neurotrophic factors Adipocyte Internal medicine medicine sympathetic innervation Brain-derived neurotrophic factor aging Cell Biology adipose tissue 030104 developmental biology Endocrinology BDNF chemistry biology.protein Neurology (clinical) Geriatrics and Gerontology 030217 neurology & neurosurgery Neurotrophin |
| Zdroj: | Aging and Disease |
| ISSN: | 2152-5250 |
| Popis: | Aging-related adipose tissue dysfunction contributes to the progression of chronic metabolic diseases. We investigated the role of age-dependent expression of a neurotrophin, brain-derived neurotrophic factor (BDNF) in adipose tissue. Pro-BDNF expression was elevated in epididymal white adipose tissue (eWAT) with advanced age, which was associated with the reduction in sympathetic innervation. Interestingly, BDNF expression was enriched in PDGFRα+ adipocyte progenitors isolated from eWAT, with age-dependent increase in expression. In vitro pro-BDNF treatment caused apoptosis in adipocytes differentiated from C3H10T1/2 cells, and siRNA knockdown of sortilin mitigated these effects. Tamoxifen-inducible PDGFRα+ cell-specific deletion of BDNF (BDNFPdgfra KO) reduced pro-BDNF expression in eWAT, prevented age-associated declines in sympathetic innervation and mitochondrial content in eWAT, and improved insulin sensitivity. Moreover, BDNFPdgfra KO mice showed reduced expression of aging-induced inflammation and senescence markers in eWAT. Collectively, these results identified the upregulation of pro-BDNF expression in adipocyte progenitors as a feature of visceral white adipose tissue aging and suggested that inhibition of BDNF expression in adipocyte progenitors is potentially beneficial to prevent aging-related adipose tissue dysfunction. |
| Databáze: | OpenAIRE |
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