Abstract
BackgroundTwist 1 is highly expressed in adipose tissue and has been associated with obesity and related disorders. However, the molecular function of Twist 1 in adipose tissue is unclear. Twist 1 has been implicated in cell lineage determination and differentiation. Therefore, we investigated both the role of Twist 1 in adipocyte precursor mobilization and the relationship of Twist 1 with other molecular determinants of adipocyte differentiation.MethodsWe examined Twist 1 mRNA and protein expression in subcutaneous adipose tissues from diet-induced obese C57/BL6 mice and Wistar rats and in obese patients undergoing liposuction or adipose transplant surgeries. Twist 1 expression was measured on days 0, 2, 4, 8, and 12 of 3T3-L1 differentiation in vitro. The role of Twist 1 in adipogenesis was explored using retroviral interference of Twist 1 expression. Adipokine secretion was evaluated using a RayBio® Biotin Label-based Adipokine Array.ResultsTwist 1 mRNA and protein levels were reduced in diet-induced obese mice and rats and in obese humans. Twist 1 was upregulated during 3T3-L1 preadipocyte differentiation in vitro, beginning from the fourth day of differentiation induction. Retroviral interference of Twist 1 expression did not significantly impair lipid formation; however, retroviral interference induced PPARγ mRNA and protein expression on day 4 of differentiation induction. Adipokine array analyses revealed increased secretion of CXCR4 (19.55-fold), VEGFR1 (92.13-fold), L-21 R (63.55-fold), and IL-12 R beta 1 (59.66-fold) and decreased secretion of VEGFR3 (0.01-fold), TSLP R (0.071-fold), MIP-1 gamma (0.069-fold), TNF RI/TNFRSF1A (0.09-fold), and MFG-E8 (0.06-fold).ConclusionsTwist 1 is a regulator of adipocyte gene expression although it is not likely to regulate differentiation. We identified PPARγ as a potential target of Twist 1 and found variation in the secretion of multiple adipokines, which might indicate a prospective mechanism linking Twist 1 expression with obesity or associated diseases.
Highlights
Twist 1 is highly expressed in adipose tissue and has been associated with obesity and related disorders
Previous studies have confirmed that the expression of PPARγ during differentiation induces the adipose phenotype, which is defined by lipid accumulation and the expression of other genes related to this process [8]
We found that Twist 1 was negatively correlated with obesity development and that retroviral interference of Twist 1 expression did not impair the process of lipid formation in cultured 3T3-L1 preadipocytes; retroviral interference of Twist 1 altered the expression of PPARγ and influenced the secretion of multiple adipokines, mainly interleukins, growth factors, chemokines, and their receptors, providing a prospective mechanism linking Twist 1 expression with obesity or obesity-associated diseases
Summary
Twist 1 is highly expressed in adipose tissue and has been associated with obesity and related disorders. Numerous factors and proteins have been implicated in the generation of new fat cells, including peroxisome proliferator-activated receptor gamma (PPARγ) [2,3], CCAAT/enhancer binding protein (C/EBP, which includes C/EBP α, C/EBP β, and C/EBP δ) [4,5], adipocyte lipid binding protein (ALBP), and adipocyte determination and differentiation factor 1 (ADD1) [6,7]. Among the three isoforms (PPAR α, β/δ, and γ) in the PPAR family, PPARγ is most specific to fat cells and exerts the strongest effect in adipogenesis. It is mainly expressed in adipose tissues and plays an important role in lipid metabolism and the adipocyte differentiation process. Studies on the transcription factors that control PPARγ expression in adipose progenitors may provide insight into adipocyte maturation in normal and obesity states
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