| Item type |
文献 / Documents(1) |
| 公開日 |
2024-07-18 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1016/j.jlr.2023.100450 |
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関連名称 |
10.1016/j.jlr.2023.100450 |
| 出版タイプ |
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出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Sphingosine kinase 1 is involved in triglyceride breakdown by maintaining lysosomal integrity in brown adipocytes |
| タイトル別表記 |
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その他のタイトル |
Lysosomal integrity requires sphingosine kinase activity |
| 著者 |
モリシゲ, ジュンイチ
ヨシオカ, カズアキ
ナカタ, ヒロキ
イシマル, カズヒロ
ナガタ, ナオト
田中, 保
タクワ, ヨウ
アンドウ, ヒトシ
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| 抄録 |
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内容記述 |
Sphingosine 1-phosphate (S1P) has been implicated in brown adipose tissue (BAT) formation and energy consumption; however, the mechanistic role of sphingolipids, including S1P, in BAT remains unclear. Here, we showed that, in mice, BAT activation by cold exposure upregulated mRNA and protein expression of the S1P-synthesizing enzyme sphingosine kinase 1 (SphK1) and S1P production in BAT. Treatment of wild-type brown adipocytes with exogenous S1P or S1P receptor subtype-selective agonists stimulated triglyceride (TG) breakdown only marginally, compared with noradrenaline. However, genetic deletion of Sphk1 resulted in hypothermia and diminished body weight loss upon cold exposure, suggesting that SphK1 is involved in thermogenesis through mechanisms different from receptor-mediated, extracellular action of S1P. In BAT of wild-type mice, SphK1 was localized largely in the lysosomes of brown adipocytes. In the brown adipocytes of Sphk1-/- mice, the number of lysosomes was reduced and lysosomal function, including proteolytic activity, acid esterase activity, and motility, was impaired. Concordantly, nuclear translocation of transcription factor EB, a master transcriptional regulator of lysosome biogenesis, was reduced, leading to decreased mRNA expression of the lysosome-related genes in Sphk1-/- BAT. Moreover, BAT of Sphk1-/-mice showed greater TG accumulation with dominant larger lipid droplets in brown adipocytes. Inhibition of lysosomes with chloroquine resulted in a less extent of triglyceride accumulation in Sphk1-/- brown adipocytes compared with wild-type brown adipocytes, suggesting a reduced lysosome-mediated TG breakdown in Sphk1-/- mice. Our results indicate a novel role of SphK1 in lysosomal integrity, which is required for TG breakdown and thermogenesis in BAT. |
| キーワード |
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|
主題 |
Adipose tissue |
| キーワード |
|
|
主題 |
brown |
| キーワード |
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|
主題 |
lipid droplets |
| キーワード |
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主題 |
lipase |
| キーワード |
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主題 |
lipolysis |
| キーワード |
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|
主題 |
lysosome |
| キーワード |
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|
主題 |
sphingolipids |
| キーワード |
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|
主題 |
sphingosine kinase |
| キーワード |
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|
主題 |
sphingosine phosphate |
| キーワード |
|
|
主題 |
thermogenesis |
| キーワード |
|
|
主題 |
triglyceride |
| 書誌情報 |
en : Journal of Lipid Research
巻 64,
号 11,
p. 100450,
発行日 2023-09-24
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
15397262 |
| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
00222275 |
| 収録物ID |
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|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00701215 |
| 出版者 |
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出版者 |
Elsevier |
| 出版者 |
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出版者 |
American Society for Biochemistry and Molecular Biology |
| 権利情報 |
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|
権利情報 |
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| EID |
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|
識別子 |
403328 |
| 言語 |
|
|
言語 |
eng |
jlr_64_11_100450.pdf (4.27 MB)
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