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
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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
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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)