Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity

Abstract In obese adipose tissue (AT), hypertrophic expansion of adipocytes is not matched by new vessel formation, leading to AT hypoxia. As a result, hypoxia inducible factor-1⍺ (HIF-1⍺) accumulates in adipocytes inducing a transcriptional program that upregulates profibrotic genes and biosyntheti...

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Autores principales:	Golnaz Anvari, Evangelia Bellas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7273b33926d641d3b27c29c221357fc2
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spelling	oai:doaj.org-article:7273b33926d641d3b27c29c221357fc22021-11-08T10:54:02ZHypoxia induces stress fiber formation in adipocytes in the early stage of obesity10.1038/s41598-021-00335-12045-2322https://doaj.org/article/7273b33926d641d3b27c29c221357fc22021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00335-1https://doaj.org/toc/2045-2322Abstract In obese adipose tissue (AT), hypertrophic expansion of adipocytes is not matched by new vessel formation, leading to AT hypoxia. As a result, hypoxia inducible factor-1⍺ (HIF-1⍺) accumulates in adipocytes inducing a transcriptional program that upregulates profibrotic genes and biosynthetic enzymes such as lysyl oxidase (LOX) synthesis. This excess synthesis and crosslinking of extracellular matrix (ECM) components cause AT fibrosis. Although fibrosis is a hallmark of obese AT, the role of fibroblasts, cells known to regulate fibrosis in other fibrosis-prone tissues, is not well studied. Here we have developed an in vitro model of AT to study adipocyte-fibroblast crosstalk in a hypoxic environment. Further, this in vitro model was used to investigate the effect of hypoxia on adipocyte mechanical properties via ras homolog gene family member A (RhoA)/Rho-associated coiled-coil kinases (ROCK) signaling pathways. We confirmed that hypoxia creates a diseased phenotype by inhibiting adipocyte maturation and inducing actin stress fiber formation facilitated by myocardin-related transcription factor A (MRTF-A/MKL1) nuclear translocation. This work presents new potential therapeutic targets for obesity by improving adipocyte maturation and limiting mechanical stress in obese AT.Golnaz AnvariEvangelia BellasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Golnaz Anvari Evangelia Bellas Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity
description	Abstract In obese adipose tissue (AT), hypertrophic expansion of adipocytes is not matched by new vessel formation, leading to AT hypoxia. As a result, hypoxia inducible factor-1⍺ (HIF-1⍺) accumulates in adipocytes inducing a transcriptional program that upregulates profibrotic genes and biosynthetic enzymes such as lysyl oxidase (LOX) synthesis. This excess synthesis and crosslinking of extracellular matrix (ECM) components cause AT fibrosis. Although fibrosis is a hallmark of obese AT, the role of fibroblasts, cells known to regulate fibrosis in other fibrosis-prone tissues, is not well studied. Here we have developed an in vitro model of AT to study adipocyte-fibroblast crosstalk in a hypoxic environment. Further, this in vitro model was used to investigate the effect of hypoxia on adipocyte mechanical properties via ras homolog gene family member A (RhoA)/Rho-associated coiled-coil kinases (ROCK) signaling pathways. We confirmed that hypoxia creates a diseased phenotype by inhibiting adipocyte maturation and inducing actin stress fiber formation facilitated by myocardin-related transcription factor A (MRTF-A/MKL1) nuclear translocation. This work presents new potential therapeutic targets for obesity by improving adipocyte maturation and limiting mechanical stress in obese AT.
format	article
author	Golnaz Anvari Evangelia Bellas
author_facet	Golnaz Anvari Evangelia Bellas
author_sort	Golnaz Anvari
title	Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity
title_short	Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity
title_full	Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity
title_fullStr	Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity
title_full_unstemmed	Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity
title_sort	hypoxia induces stress fiber formation in adipocytes in the early stage of obesity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7273b33926d641d3b27c29c221357fc2
work_keys_str_mv	AT golnazanvari hypoxiainducesstressfiberformationinadipocytesintheearlystageofobesity AT evangeliabellas hypoxiainducesstressfiberformationinadipocytesintheearlystageofobesity
_version_	1718442536610037760

Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity

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