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Title: The Mevalonate Pathway Is Indispensable for Adipocyte Survival
Authors: Yeh, Yu-Sheng
Jheng, Huei-Fen  kyouindb  KAKEN_id
Iwase, Mari
Kim, Minji
Mohri, Shinsuke
Kwon, Jungin
Kawarasaki, Satoko
Li, Yongjia
Takahashi, Haruya  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-3182-2894 (unconfirmed)
Ara, Takeshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-1754-2837 (unconfirmed)
Nomura, Wataru  kyouindb  KAKEN_id
Kawada, Teruo
Goto, Tsuyoshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-1283-147X (unconfirmed)
Author's alias: 鄭, 蕙芬
岩瀬, 麻里
毛利, 晋輔
權, 庭仁
川原崎, 聡子
高橋, 春弥
荒, 武
野村, 亘
河田, 照雄
後藤, 剛
Issue Date: 30-Nov-2018
Publisher: Elsevier BV
Journal title: iScience
Volume: 9
Start page: 175
End page: 191
Abstract: The mevalonate pathway is essential for the synthesis of isoprenoids and cholesterol. Adipose tissue is known as a major site for cholesterol storage; however, the role of the local mevalonate pathway and its synthesized isoprenoids remains unclear. In this study, adipose-specific mevalonate pathway-disrupted (aKO) mice were generated through knockout of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR). aKO mice showed serious lipodystrophy accompanied with glucose and lipid metabolic disorders and hepatomegaly. These metabolic variations in aKO mice were dramatically reversed after fat transplantation. In addition, HMGCR-disrupted adipocytes exhibited loss of lipid accumulation and an increase of cell death, which were ameliorated by the supplementation of mevalonate and geranylgeranyl pyrophosphate but not farnesyl pyrophosphate and squalene. Finally, we found that apoptosis may be involved in adipocyte death induced by HMGCR down-regulation. Our findings indicate that the mevalonate pathway is essential for adipocytes and further suggest that this pathway is an important regulator of adipocyte turnover.
Rights: © 2018 The Authors.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/2433/246434
DOI(Published Version): 10.1016/j.isci.2018.10.019
PubMed ID: 30396151
Appears in Collections:Journal Articles

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