Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 Shedding

Abnormal adipogenesis regulation is accompanied by a variety of metabolic dysfunctions and disorders. Caveolae play an important role in the regulation of fat production, modulated by caveolae-associated proteins (Cavin-1 to 4). Here, we investigated the role of Cavin-3 in lipogenesis and adipocyte...

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Main Authors: Phil June Park, Sung Tae Kim
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/14/5000
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author Phil June Park
Sung Tae Kim
author_facet Phil June Park
Sung Tae Kim
author_sort Phil June Park
collection DOAJ
description Abnormal adipogenesis regulation is accompanied by a variety of metabolic dysfunctions and disorders. Caveolae play an important role in the regulation of fat production, modulated by caveolae-associated proteins (Cavin-1 to 4). Here, we investigated the role of Cavin-3 in lipogenesis and adipocyte differentiation, as the regulatory functions and roles of Cavin-3 in adipocytes are unknown. A Cavin-3 knockdown/overexpression stable cell line was established, and adipogenesis-related gene and protein expression changes were investigated by real-time quantitative PCR and Western blot analysis, respectively. Additionally, confocal immune-fluorescence microscopy was used to verify the intracellular position of the relevant factors. The results showed that Cavin-3 mRNA and protein expression were elevated, along with physiological factors such as lipid droplet formation, during adipogenesis. Cavin-3 silencing resulted in retarded adipocyte differentiation, and its overexpression accelerated this process. Furthermore, Cavin-3 knockdown resulted in decreased expression of adipogenesis-related genes, such as <i>PPAR-γ, FAS, aP2</i>, and <i>Adipoq</i>, whereas preadipocyte factor-1 (<i>Pref-1</i>) was markedly increased during adipocyte maturation. Overall, Cavin-3 influences caveolar stability and modulates the tumor necrosis factor-alpha-converting enzyme (TACE)-mediated Pref-1 shedding process in both mouse and human adipocytes. The Cavin-3-dependent shedding mechanism appears to be an important process in adipocyte maturation, providing a potential therapeutic target for obesity-related disorders.
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spelling doaj.art-57664152e99443b2b734d03d4b1a67232023-11-20T06:51:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114500010.3390/ijms21145000Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 SheddingPhil June Park0Sung Tae Kim1Bioscience Laboratory, AMOREPACIFIC R&D Center, 1920 Yonggu-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17074, KoreaDepartment of Pharmaceutical Engineering, Inje University, 197 Inje-ro, Gimhae-si, Gyeongsangnam-do 50834, KoreaAbnormal adipogenesis regulation is accompanied by a variety of metabolic dysfunctions and disorders. Caveolae play an important role in the regulation of fat production, modulated by caveolae-associated proteins (Cavin-1 to 4). Here, we investigated the role of Cavin-3 in lipogenesis and adipocyte differentiation, as the regulatory functions and roles of Cavin-3 in adipocytes are unknown. A Cavin-3 knockdown/overexpression stable cell line was established, and adipogenesis-related gene and protein expression changes were investigated by real-time quantitative PCR and Western blot analysis, respectively. Additionally, confocal immune-fluorescence microscopy was used to verify the intracellular position of the relevant factors. The results showed that Cavin-3 mRNA and protein expression were elevated, along with physiological factors such as lipid droplet formation, during adipogenesis. Cavin-3 silencing resulted in retarded adipocyte differentiation, and its overexpression accelerated this process. Furthermore, Cavin-3 knockdown resulted in decreased expression of adipogenesis-related genes, such as <i>PPAR-γ, FAS, aP2</i>, and <i>Adipoq</i>, whereas preadipocyte factor-1 (<i>Pref-1</i>) was markedly increased during adipocyte maturation. Overall, Cavin-3 influences caveolar stability and modulates the tumor necrosis factor-alpha-converting enzyme (TACE)-mediated Pref-1 shedding process in both mouse and human adipocytes. The Cavin-3-dependent shedding mechanism appears to be an important process in adipocyte maturation, providing a potential therapeutic target for obesity-related disorders.https://www.mdpi.com/1422-0067/21/14/5000adipogenesis3T3-L1 adipocytesCavin-3Pref-1
spellingShingle Phil June Park
Sung Tae Kim
Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 Shedding
International Journal of Molecular Sciences
adipogenesis
3T3-L1 adipocytes
Cavin-3
Pref-1
title Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 Shedding
title_full Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 Shedding
title_fullStr Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 Shedding
title_full_unstemmed Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 Shedding
title_short Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 Shedding
title_sort caveolae associated protein 3 cavin 3 influences adipogenesis via tace mediated pref 1 shedding
topic adipogenesis
3T3-L1 adipocytes
Cavin-3
Pref-1
url https://www.mdpi.com/1422-0067/21/14/5000
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