| First Author | Song HD | Year | 2020 |
| Journal | Aging Dis | Volume | 11 |
| Issue | 3 | Pages | 575-587 |
| PubMed ID | 32489703 | Mgi Jnum | J:298213 |
| Mgi Id | MGI:6477446 | Doi | 10.14336/AD.2019.0810 |
| Citation | Song HD, et al. (2020) Aging-Induced Brain-Derived Neurotrophic Factor in Adipocyte Progenitors Contributes to Adipose Tissue Dysfunction. Aging Dis 11(3):575-587 |
| abstractText | 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 PDGFRalpha(+) 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 PDGFRalpha(+) cell-specific deletion of BDNF (BDNF(Pdgfra) KO) reduced pro-BDNF expression in eWAT, prevented age-associated declines in sympathetic innervation and mitochondrial content in eWAT, and improved insulin sensitivity. Moreover, BDNF(Pdgfra) 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. |
