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Survivin is essential for thermogenic program and metabolic homeostasis in mice

OBJECTIVE: Survivin is a member of the inhibitor of apoptosis family. Our previous study showed that survivin expression could be strongly induced by long-term, high-fat diet (HFD) exposure in vivo. It could also be induced by insulin through the PI3K/mTOR signaling pathway in vitro. Therefore, we h...

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Autores principales: Alimujiang, Miriayi, Sun, Jingjing, Chen, Shuqing, Bai, Ningning, Chen, Shuqin, Hu, Fan, Ma, Jingyuan, Xu, Yuejie, Xu, Jun, Ma, Xiaojing, Yang, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866150/
https://www.ncbi.nlm.nih.gov/pubmed/35114418
http://dx.doi.org/10.1016/j.molmet.2022.101446
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author Alimujiang, Miriayi
Sun, Jingjing
Chen, Shuqing
Bai, Ningning
Chen, Shuqin
Hu, Fan
Ma, Jingyuan
Xu, Yuejie
Xu, Jun
Ma, Xiaojing
Yang, Ying
author_facet Alimujiang, Miriayi
Sun, Jingjing
Chen, Shuqing
Bai, Ningning
Chen, Shuqin
Hu, Fan
Ma, Jingyuan
Xu, Yuejie
Xu, Jun
Ma, Xiaojing
Yang, Ying
author_sort Alimujiang, Miriayi
collection PubMed
description OBJECTIVE: Survivin is a member of the inhibitor of apoptosis family. Our previous study showed that survivin expression could be strongly induced by long-term, high-fat diet (HFD) exposure in vivo. It could also be induced by insulin through the PI3K/mTOR signaling pathway in vitro. Therefore, we hypothesized that under certain conditions, survivin expression might be required for adipocyte function. In the current study, we aim to further investigate the regulation of survivin expression in mature adipocytes upon various nutritional stimuli and the role of survivin using adipocyte-specific survivin knockout (SKO) mice. METHODS: SKO mice were obtained by crossing survivin(flox/flox) mice with Adiponectin-Cre(+/-) mice. The overall metabolic phenotype was observed under chow diet (CD) and HFD feeding conditions. The thermogenic program of mice was detected upon cold exposure. The inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT) stromal vascular fraction cells were isolated and differentiated into mature adipocytes, and the effects of survivin deletion on mature adipocyte function were detected in vitro. RESULTS: Survivin expression in adipose tissue and adipocytes was regulated by short-term nutritional stress both in vivo and in vitro. The postnatal development of BAT was impaired in SKO mice, which resulted in drastically reduced BAT mass and decreased expression of the thermogenic protein Ucp1 in 24-week-old mice fed with CD. After HFD feeding, the iWAT and BAT mass of SKO mice were significantly decreased, causing ectopic lipid accumulation in the liver, which was associated with insulin resistance and glucose intolerance. Upon cold exposure, the expression of thermogenic genes and proteins was markedly reduced in BAT and iWAT of SKO mice, accompanied by abnormal mitochondrial structure and induced autophagy. Consistently, thermogenic program and mitochondrial oxidative phosphorylation were reduced in survivin-depleted brown and beige adipocytes in vitro. CONCLUSIONS: Our findings showed that survivin could be regulated by nutritional stress in adipocytes and revealed a new role of survivin in maintaining normal BAT mass and positively regulating the thermogenic program and mitochondrial oxidative phosphorylation.
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spelling pubmed-88661502022-03-02 Survivin is essential for thermogenic program and metabolic homeostasis in mice Alimujiang, Miriayi Sun, Jingjing Chen, Shuqing Bai, Ningning Chen, Shuqin Hu, Fan Ma, Jingyuan Xu, Yuejie Xu, Jun Ma, Xiaojing Yang, Ying Mol Metab Original Article OBJECTIVE: Survivin is a member of the inhibitor of apoptosis family. Our previous study showed that survivin expression could be strongly induced by long-term, high-fat diet (HFD) exposure in vivo. It could also be induced by insulin through the PI3K/mTOR signaling pathway in vitro. Therefore, we hypothesized that under certain conditions, survivin expression might be required for adipocyte function. In the current study, we aim to further investigate the regulation of survivin expression in mature adipocytes upon various nutritional stimuli and the role of survivin using adipocyte-specific survivin knockout (SKO) mice. METHODS: SKO mice were obtained by crossing survivin(flox/flox) mice with Adiponectin-Cre(+/-) mice. The overall metabolic phenotype was observed under chow diet (CD) and HFD feeding conditions. The thermogenic program of mice was detected upon cold exposure. The inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT) stromal vascular fraction cells were isolated and differentiated into mature adipocytes, and the effects of survivin deletion on mature adipocyte function were detected in vitro. RESULTS: Survivin expression in adipose tissue and adipocytes was regulated by short-term nutritional stress both in vivo and in vitro. The postnatal development of BAT was impaired in SKO mice, which resulted in drastically reduced BAT mass and decreased expression of the thermogenic protein Ucp1 in 24-week-old mice fed with CD. After HFD feeding, the iWAT and BAT mass of SKO mice were significantly decreased, causing ectopic lipid accumulation in the liver, which was associated with insulin resistance and glucose intolerance. Upon cold exposure, the expression of thermogenic genes and proteins was markedly reduced in BAT and iWAT of SKO mice, accompanied by abnormal mitochondrial structure and induced autophagy. Consistently, thermogenic program and mitochondrial oxidative phosphorylation were reduced in survivin-depleted brown and beige adipocytes in vitro. CONCLUSIONS: Our findings showed that survivin could be regulated by nutritional stress in adipocytes and revealed a new role of survivin in maintaining normal BAT mass and positively regulating the thermogenic program and mitochondrial oxidative phosphorylation. Elsevier 2022-01-31 /pmc/articles/PMC8866150/ /pubmed/35114418 http://dx.doi.org/10.1016/j.molmet.2022.101446 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Alimujiang, Miriayi
Sun, Jingjing
Chen, Shuqing
Bai, Ningning
Chen, Shuqin
Hu, Fan
Ma, Jingyuan
Xu, Yuejie
Xu, Jun
Ma, Xiaojing
Yang, Ying
Survivin is essential for thermogenic program and metabolic homeostasis in mice
title Survivin is essential for thermogenic program and metabolic homeostasis in mice
title_full Survivin is essential for thermogenic program and metabolic homeostasis in mice
title_fullStr Survivin is essential for thermogenic program and metabolic homeostasis in mice
title_full_unstemmed Survivin is essential for thermogenic program and metabolic homeostasis in mice
title_short Survivin is essential for thermogenic program and metabolic homeostasis in mice
title_sort survivin is essential for thermogenic program and metabolic homeostasis in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866150/
https://www.ncbi.nlm.nih.gov/pubmed/35114418
http://dx.doi.org/10.1016/j.molmet.2022.101446
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