Rosiglitazone drives cavin-2/SDPR expression in adipocytes in a CEBPα-dependent manner

Abstract

Caveolae are abundant adipocyte surface domains involved in insulin signaling, membrane trafficking and lipid homeostasis. Transcriptional control mechanisms for caveolins and cavins, the building blocks of caveolae, are thus arguably important for adipocyte biology and studies in this area may give insight into insulin resistance and diabetes. Here we addressed the hypothesis that one of the less characterized caveolar components, cavin-2 (SDPR), is controlled by CCAAT/Enhancer Binding Protein (CEBPα) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG). Using human mRNA expression data we found that SDPR correlated with PPARG in several tissues. This was also observed during differentiation of 3T3-L1 fibroblasts into adipocytes. Treatment of 3T3-L1-derived adipocytes with the PPARγ-activator Rosiglitazone increased SDPR and CEBPα expression at both the mRNA and protein levels. Silencing of CEBPα antagonized these effects. Further, adenoviral expression of PPARγ/CEBPα or Rosiglitazone-treatment increased SDPR expression in primary rat adipocytes. The myocardin family coactivator MKL1 was recently shown to regulate SDPR expression in human coronary artery smooth muscle cells. However, we found that actin depolymerization, known to inhibit MKL1 and MKL2, was without effect on SDPR mRNA levels in adipocytes, even though overexpression of MKL1 and MKL2 had the capacity to increase caveolins and cavins and to repress PPARγ/CEBPα. Altogether, this work demonstrates that CEBPα expression and PPARγ-activity promote SDPR transcription and further supports the emerging notion that PPARγ/CEBPα and MKL1/MKL2 are antagonistic in adipocytes.

Requirement of Cavin-2 for the expression and stability of IRβ in adequate adipocyte differentiation

“…A recent study showed that the expression of CEBPα and PPARγ activity promote the transcription of Cavin-2 during adipogenesis [ 24 ]. To demonstrate that IR/Akt signaling is involved in the transcription of Cavin-2, we investigated the effect of an Akt inhibitor on its transcription.…”

“…Cavin-2 is highly expressed in the adipose tissue, lung, and heart [ [21] , [22] , [23] ]. A recent study showed that the expression level of Cavin-2 mRNA is positively correlated with those of PPARγ and C/EBPα [ 24 ]. This suggests that Cavin-2 might play a pivotal role in the differentiation and/or maturation of adipocytes, however, the role of Cavin-2 in adipocyte differentiation and lipid metabolism remains unknown.…”

A New Symmetrical Thiazolidinedione Derivative: In Silico Design, Synthesis, and In Vivo Evaluation on a Streptozotocin-Induced Rat Model of Diabetes

“…Compared to the untreated diabetic animals, the 2-week administration of 1G or PIO significantly lowered levels of TNF-α (Figure 11a) and IL-6 (Figure 11b), cytokines known to play an important role in the mechanism of metabolic and oxidative damage, especially in adipocytes. The development of diabetes and obesity is associated with impaired adipose tissue function [1,49]. A higher ROS production causes high levels of TNF-α, which mediates liver injury [44] and increases insulin resistance [24], leading to greater inflammation.…”

Rosiglitazone Enhances Browning Adipocytes in Association with MAPK and PI3-K Pathways During the Differentiation of Telomerase-Transformed Mesenchymal Stromal Cells into Adipocytes

“…PPAR-γ along with C/EBP-α are key players in adipogenic differentiation that crosstalk and overlap to regulate the expression of target genes [17,26,29,30,31]. Their expression occurs at the late adipogenic stage and in mature adipocytes; these expressions are maintained in a positive feedback loop to preserve the phenotype of the mature adipocyte [29].…”