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Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue

White adipocytes act as lipid storage, and play an important role in energy homeostasis. The small GTPase Rac1 has been implicated in the regulation of insulin-stimulated glucose uptake in white adipocytes. Adipocyte-specific rac1-knockout (adipo-rac1-KO) mice exhibit atrophy of subcutaneous and epi...

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Autores principales: Hasegawa, Kiko, Takenaka, Nobuyuki, Yamamoto, Maaya, Sakoda, Yoshiki, Aiba, Atsu, Satoh, Takaya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003776/
https://www.ncbi.nlm.nih.gov/pubmed/36902044
http://dx.doi.org/10.3390/ijms24054608
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author Hasegawa, Kiko
Takenaka, Nobuyuki
Yamamoto, Maaya
Sakoda, Yoshiki
Aiba, Atsu
Satoh, Takaya
author_facet Hasegawa, Kiko
Takenaka, Nobuyuki
Yamamoto, Maaya
Sakoda, Yoshiki
Aiba, Atsu
Satoh, Takaya
author_sort Hasegawa, Kiko
collection PubMed
description White adipocytes act as lipid storage, and play an important role in energy homeostasis. The small GTPase Rac1 has been implicated in the regulation of insulin-stimulated glucose uptake in white adipocytes. Adipocyte-specific rac1-knockout (adipo-rac1-KO) mice exhibit atrophy of subcutaneous and epididymal white adipose tissue (WAT); white adipocytes in these mice are significantly smaller than controls. Here, we aimed to investigate the mechanisms underlying the aberrations in the development of Rac1-deficient white adipocytes by employing in vitro differentiation systems. Cell fractions containing adipose progenitor cells were obtained from WAT and subjected to treatments that induced differentiation into adipocytes. In concordance with observations in vivo, the generation of lipid droplets was significantly attenuated in Rac1-deficient adipocytes. Notably, the induction of various enzymes responsible for de novo synthesis of fatty acids and triacylglycerol in the late stage of adipogenic differentiation was almost completely suppressed in Rac1-deficient adipocytes. Furthermore, the expression and activation of transcription factors, such as the CCAAT/enhancer-binding protein (C/EBP) β, which is required for the induction of lipogenic enzymes, were largely inhibited in Rac1-deficient cells in both early and late stages of differentiation. Altogether, Rac1 is responsible for adipogenic differentiation, including lipogenesis, through the regulation of differentiation-related transcription.
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spelling pubmed-100037762023-03-11 Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue Hasegawa, Kiko Takenaka, Nobuyuki Yamamoto, Maaya Sakoda, Yoshiki Aiba, Atsu Satoh, Takaya Int J Mol Sci Article White adipocytes act as lipid storage, and play an important role in energy homeostasis. The small GTPase Rac1 has been implicated in the regulation of insulin-stimulated glucose uptake in white adipocytes. Adipocyte-specific rac1-knockout (adipo-rac1-KO) mice exhibit atrophy of subcutaneous and epididymal white adipose tissue (WAT); white adipocytes in these mice are significantly smaller than controls. Here, we aimed to investigate the mechanisms underlying the aberrations in the development of Rac1-deficient white adipocytes by employing in vitro differentiation systems. Cell fractions containing adipose progenitor cells were obtained from WAT and subjected to treatments that induced differentiation into adipocytes. In concordance with observations in vivo, the generation of lipid droplets was significantly attenuated in Rac1-deficient adipocytes. Notably, the induction of various enzymes responsible for de novo synthesis of fatty acids and triacylglycerol in the late stage of adipogenic differentiation was almost completely suppressed in Rac1-deficient adipocytes. Furthermore, the expression and activation of transcription factors, such as the CCAAT/enhancer-binding protein (C/EBP) β, which is required for the induction of lipogenic enzymes, were largely inhibited in Rac1-deficient cells in both early and late stages of differentiation. Altogether, Rac1 is responsible for adipogenic differentiation, including lipogenesis, through the regulation of differentiation-related transcription. MDPI 2023-02-27 /pmc/articles/PMC10003776/ /pubmed/36902044 http://dx.doi.org/10.3390/ijms24054608 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hasegawa, Kiko
Takenaka, Nobuyuki
Yamamoto, Maaya
Sakoda, Yoshiki
Aiba, Atsu
Satoh, Takaya
Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue
title Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue
title_full Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue
title_fullStr Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue
title_full_unstemmed Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue
title_short Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue
title_sort regulation of de novo lipid synthesis by the small gtpase rac1 in the adipogenic differentiation of progenitor cells from mouse white adipose tissue
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003776/
https://www.ncbi.nlm.nih.gov/pubmed/36902044
http://dx.doi.org/10.3390/ijms24054608
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