Aging-induced brain-derived neurotrophic factor in adipocyte progenitors contributes to adipose tissue dysfunction

Hyun Doo Song; Sang Nam Kim; Abhirup Saha; Sang Yeop Ahn; Seun Akindehin; Yeonho Son; Yoon Keun Cho; Min Su Kim; Ji Hyun Park; Young Suk Jung; Yun Hee Lee

doi:10.14336/AD.2019.0810

Aging-induced brain-derived neurotrophic factor in adipocyte progenitors contributes to adipose tissue dysfunction

Hyun Doo Song, Sang Nam Kim, Abhirup Saha, Sang Yeop Ahn, Seun Akindehin, Yeonho Son, Yoon Keun Cho, Min Su Kim, Ji Hyun Park, Young Suk Jung, Yun Hee Lee

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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 sortilinmitigated these effects. Tamoxifen-inducible PDGFRα⁺ 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.

Original language	English
Pages (from-to)	575-587
Number of pages	13
Journal	Aging and Disease
Volume	11
Issue number	3
DOIs	https://doi.org/10.14336/AD.2019.0810
Publication status	Published - 2020

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2014R1A6A3A04056472, 2019R1C1C1002014, 2018 R1A5A2024425) and the Bio & Medical Technology Development Program of the NRF funded by the Korean government (MSIP&MOHW) (No. NRF-2016M3A9D 5A01953818, 2013M3A9D5072550))

Publisher Copyright:
© 2019 Song H. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

All Science Journal Classification (ASJC) codes

Pathology and Forensic Medicine
Geriatrics and Gerontology
Clinical Neurology
Cell Biology

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10.14336/AD.2019.0810

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@article{d0102f9c389b4be5abe018b64b67016d,

title = "Aging-induced brain-derived neurotrophic factor in adipocyte progenitors contributes to adipose tissue dysfunction",

abstract = "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 sortilinmitigated 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.",

author = "Song, {Hyun Doo} and Kim, {Sang Nam} and Abhirup Saha and Ahn, {Sang Yeop} and Seun Akindehin and Yeonho Son and Cho, {Yoon Keun} and Kim, {Min Su} and Park, {Ji Hyun} and Jung, {Young Suk} and Lee, {Yun Hee}",

note = "Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2014R1A6A3A04056472, 2019R1C1C1002014, 2018 R1A5A2024425) and the Bio & Medical Technology Development Program of the NRF funded by the Korean government (MSIP&MOHW) (No. NRF-2016M3A9D 5A01953818, 2013M3A9D5072550)) Publisher Copyright: {\textcopyright} 2019 Song H. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2020",

doi = "10.14336/AD.2019.0810",

language = "English",

volume = "11",

pages = "575--587",

journal = "Aging and Disease",

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T1 - Aging-induced brain-derived neurotrophic factor in adipocyte progenitors contributes to adipose tissue dysfunction

AU - Song, Hyun Doo

AU - Kim, Sang Nam

AU - Saha, Abhirup

AU - Ahn, Sang Yeop

AU - Akindehin, Seun

AU - Son, Yeonho

AU - Cho, Yoon Keun

AU - Kim, Min Su

AU - Park, Ji Hyun

AU - Jung, Young Suk

AU - Lee, Yun Hee

N1 - Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2014R1A6A3A04056472, 2019R1C1C1002014, 2018 R1A5A2024425) and the Bio & Medical Technology Development Program of the NRF funded by the Korean government (MSIP&MOHW) (No. NRF-2016M3A9D 5A01953818, 2013M3A9D5072550)) Publisher Copyright: © 2019 Song H. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2020

Y1 - 2020

N2 - 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 sortilinmitigated 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.

AB - 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 sortilinmitigated 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.

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DO - 10.14336/AD.2019.0810

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Aging-induced brain-derived neurotrophic factor in adipocyte progenitors contributes to adipose tissue dysfunction

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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