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Twist 1 regulates the expression of PPARγ during hormone-induced 3T3-L1 preadipocyte differentiation: a possible role in obesity and associated diseases.

Ma W, Lu S, Sun T, Wang X, Ma Y, Zhang X, Zhao R, Wang Y - Lipids Health Dis (2014)

Bottom Line: Twist 1 mRNA and protein levels were reduced in diet-induced obese mice and rats and in obese humans.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).

View Article: PubMed Central - PubMed

Affiliation: Medical Research & Laboratory Diagnostic Center, Jinan Center Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P,R, China. mwsqianyi@163.com.

ABSTRACT

Background: Twist 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.

Methods: We 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.

Results: Twist 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).

Conclusions: Twist 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.

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A model for possible role of Twist 1 in obesity or obesity-related diseases. The expression of Twist 1 influences the transcription and protein expression of PPARγ during differentiation induction and alters the secretion of multiple adipokines into the medium, either directly or indirectly. Then, altered PPARγ or adipokines play roles in obesity-related physiological process, but not in adipogenesis, which further regulates obesity or obesity-related diseases.
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Fig8: A model for possible role of Twist 1 in obesity or obesity-related diseases. The expression of Twist 1 influences the transcription and protein expression of PPARγ during differentiation induction and alters the secretion of multiple adipokines into the medium, either directly or indirectly. Then, altered PPARγ or adipokines play roles in obesity-related physiological process, but not in adipogenesis, which further regulates obesity or obesity-related diseases.

Mentions: This study had some limitations. For example, it is not clear whether Twist 1 directly regulates PPARγ expression or how PPARγ acts as a molecular bridge among the Twist 1-related processes in obesity. The pathway from Twist 1 expression to alterations in the secretion of multiple adipokines is also not clear. Repeated analyses of the adipokine array are important; however, these were not completed in the current study because of funding limitations. These limitations indicate potential avenues for our future studies.We showed that retroviral interference of Twist 1 expression induced the expression of PPARγ during differentiation induction and altered the secretion of multiple adipokines, including interleukin, growth factors, chemokines, and their receptors; however, the interference did not significantly impair the process of lipid formation. These results indicate the existence of a potential mechanism linking Twist 1 expression and obesity or obesity-associated diseases (Figure 8).Figure 8


Twist 1 regulates the expression of PPARγ during hormone-induced 3T3-L1 preadipocyte differentiation: a possible role in obesity and associated diseases.

Ma W, Lu S, Sun T, Wang X, Ma Y, Zhang X, Zhao R, Wang Y - Lipids Health Dis (2014)

A model for possible role of Twist 1 in obesity or obesity-related diseases. The expression of Twist 1 influences the transcription and protein expression of PPARγ during differentiation induction and alters the secretion of multiple adipokines into the medium, either directly or indirectly. Then, altered PPARγ or adipokines play roles in obesity-related physiological process, but not in adipogenesis, which further regulates obesity or obesity-related diseases.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150960&req=5

Fig8: A model for possible role of Twist 1 in obesity or obesity-related diseases. The expression of Twist 1 influences the transcription and protein expression of PPARγ during differentiation induction and alters the secretion of multiple adipokines into the medium, either directly or indirectly. Then, altered PPARγ or adipokines play roles in obesity-related physiological process, but not in adipogenesis, which further regulates obesity or obesity-related diseases.
Mentions: This study had some limitations. For example, it is not clear whether Twist 1 directly regulates PPARγ expression or how PPARγ acts as a molecular bridge among the Twist 1-related processes in obesity. The pathway from Twist 1 expression to alterations in the secretion of multiple adipokines is also not clear. Repeated analyses of the adipokine array are important; however, these were not completed in the current study because of funding limitations. These limitations indicate potential avenues for our future studies.We showed that retroviral interference of Twist 1 expression induced the expression of PPARγ during differentiation induction and altered the secretion of multiple adipokines, including interleukin, growth factors, chemokines, and their receptors; however, the interference did not significantly impair the process of lipid formation. These results indicate the existence of a potential mechanism linking Twist 1 expression and obesity or obesity-associated diseases (Figure 8).Figure 8

Bottom Line: Twist 1 mRNA and protein levels were reduced in diet-induced obese mice and rats and in obese humans.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).

View Article: PubMed Central - PubMed

Affiliation: Medical Research & Laboratory Diagnostic Center, Jinan Center Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P,R, China. mwsqianyi@163.com.

ABSTRACT

Background: Twist 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.

Methods: We 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.

Results: Twist 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).

Conclusions: Twist 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.

Show MeSH
Related in: MedlinePlus