A possible regulatory link between Twist 1 and PPARγ gene regulation in 3T3-L1 adipocytes

Lipids in Health and Disease, Nov 2016

Background Peroxisome proliferator-activated receptor γ (PPARγ) is a critical gene that regulates the function of adipocytes. Therefore, studies on the molecular regulation mechanism of PPARγ are important to understand the function of adipose tissue. Twist 1 is another important functional gene in adipose tissue, and hundreds of genes are regulated by Twist 1. The aim of this study was to investigate the regulation of Twist 1 and PPARγ expression in 3T3-L1 mature adipocytes. Methods We induced differentiation in 3T3-L1 preadipocytes and examined alterations in Twist 1 and PPARγ expression. We used the PPARγ agonist pioglitazone and the PPARγ antagonist T0070907 to investigate the effect of PPARγ on Twist 1 expression. In addition, we utilized retroviral interference and overexpression of Twist 1 to determine the effects of Twist 1 on PPARγ expression. Results The expression levels of Twist 1 and PPARγ were induced during differentiation in 3T3-L1 adipocytes. Application of either a PPARγ agonist (pioglitazone) or antagonist (T0070907) influenced Twist 1 expression, with up-regulation of Twist 1 under pioglitazone (1 μM, 24 h) and down-regulation of Twist 1 under T0070907 (100 μM, 24 h) exposure. Furthermore, the retroviral interference of Twist 1 decreased the protein and mRNA expression of PPARγ, while Twist 1 overexpression had the opposite effect. Conclusions There was a possible regulatory link between Twist 1 and PPARγ in 3T3-L1 mature adipocytes. This regulatory link enhanced the regulation of PPARγ and may be a functional mechanism of Twist 1 regulation of adipocyte physiology and pathology.

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A possible regulatory link between Twist 1 and PPARγ gene regulation in 3T3-L1 adipocytes

Ren et al. Lipids in Health and Disease A possible regulatory link between Twist 1 and PPARγ gene regulation in 3T3-L1 adipocytes Rui Ren 0 2 Zhufeng Chen 0 2 Xia Zhao 0 2 Tao Sun 0 2 Yuchao Zhang 1 Jie Chen 0 2 Sumei Lu 0 2 Wanshan Ma 0 2 0 Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University , Jinan, Shandong 250014 , People's Republic of China 1 Department of Endocrinology, Qingdao Municipal Hospital , Qingdao 266071 , People's Republic of China 2 Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University , Jinan, Shandong 250014 , People's Republic of China Background: Peroxisome proliferator-activated receptor γ (PPARγ) is a critical gene that regulates the function of adipocytes. Therefore, studies on the molecular regulation mechanism of PPARγ are important to understand the function of adipose tissue. Twist 1 is another important functional gene in adipose tissue, and hundreds of genes are regulated by Twist 1. The aim of this study was to investigate the regulation of Twist 1 and PPARγ expression in 3T3-L1 mature adipocytes. Methods: We induced differentiation in 3T3-L1 preadipocytes and examined alterations in Twist 1 and PPARγ expression. We used the PPARγ agonist pioglitazone and the PPARγ antagonist T0070907 to investigate the effect of PPARγ on Twist 1 expression. In addition, we utilized retroviral interference and overexpression of Twist 1 to determine the effects of Twist 1 on PPARγ expression. Results: The expression levels of Twist 1 and PPARγ were induced during differentiation in 3T3-L1 adipocytes. Application of either a PPARγ agonist (pioglitazone) or antagonist (T0070907) influenced Twist 1 expression, with up-regulation of Twist 1 under pioglitazone (1 μM, 24 h) and down-regulation of Twist 1 under T0070907 (100 μM, 24 h) exposure. Furthermore, the retroviral interference of Twist 1 decreased the protein and mRNA expression of PPARγ, while Twist 1 overexpression had the opposite effect. Conclusions: There was a possible regulatory link between Twist 1 and PPARγ in 3T3-L1 mature adipocytes. This regulatory link enhanced the regulation of PPARγ and may be a functional mechanism of Twist 1 regulation of adipocyte physiology and pathology. Twist 1; PPAR γ; Adipose tissue; Gene regulation - Background Adipose tissue is one of the most important functional organs in the human body and plays a critical role in human health. Adipose dysfunction is closely related to the occurrence and development of several diseases, including obesity, diabetes, insulin resistance and inflammation [1–3]. A number of genes are involved in the regulation of adipose function; however, the complex relationship between these genes has not been fully elucidated [4, 5]. Therefore, it is important to explore the regulation and function of key genes involved in adipose function. Peroxisome proliferator-activated receptor γ (PPARγ) is a critical gene in the regulation of adipose function. Studies have shown that PPARγ is involved in several physiological functions of adipose, including adipocyte differentiation [6–8], adipokine secretion [9, 10], adipose tissue inflammation [11] and insulin sensitivity [12]. Therefore, investigating the regulation of PPARγ is important to further understand adipose function. Twist 1 is a well-conserved transcription factor that belongs to the basic helix-loop-helix (bHLH) family. Twist 1 has been shown to be important for the formation of adipose tissue, and recently, several studies have investigated the role of Twist 1 in adipose dysfunction. Twist 1 expression in subcutaneous adipose tissue and visceral adipose tissue is related to the pathogenesis of several metabolic © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. syndromes, including obesity, inflammation and insulin resistance [13–15]. Therefore, PPARγ and Twist 1 are two genes with multiple similar functional roles in the regulation of adipose tissue. However, it is unclear whether there is an interaction between Twist 1 and PPARγ in the functional regulation of adipose tissue. Recent studies have found that the function of Twist 1 in adipose tissue is closely related to PPAR family members. Twist 1 has been shown to be a PPAR delta-inducible, negative-feedback regulator of PGC-1 in brown fat metabolism, which has important implications for understanding metabolic control and metabolic d (...truncated)


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Rui Ren, Zhufeng Chen, Xia Zhao, Tao Sun, Yuchao Zhang, Jie Chen, Sumei Lu, Wanshan Ma. A possible regulatory link between Twist 1 and PPARγ gene regulation in 3T3-L1 adipocytes, Lipids in Health and Disease, 2016, pp. 189, 15, DOI: 10.1186/s12944-016-0361-x