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

Abstract

Obesity is a major risk for diabetes. Brown adipose tissue (BAT) mediates production of heat while white adipose tissue (WAT) function in the storage of fat. Roles of BAT in the treatment of obesity and related disorders warrants more investigation. Peroxisome proliferator activator receptor gamma (PPAR-γ) is the master regulator of both BAT and WAT adipogenesis and has roles in glucose and fatty acid metabolism. Adipose tissue is the major expression site for PPAR-γ. In this study, the effects of rosiglitazone on the brown adipogenesis and the association of MAPK and PI3K pathways was investigated during the in vitro adipogenic differentiation of telomerase transformed mesenchymal stromal cells (iMSCs). Our data indicate that 2 µM rosiglitazone enhanced adipogenesis by over-expression of PPAR-γ and C/EBP-α. More specifically, brown adipogenesis was enhanced by the upregulation of EBF2 and UCP-1 and evidenced by multilocular fatty droplets morphology of the differentiated adipocytes. We also found that rosiglitazone significantly activated MAPK and PI3K pathways at the maturation stage of differentiation. Overall, the results indicate that rosiglitazone induced overexpression of PPAR-γ that in turn enhanced adipogenesis, particularly browning adipogenesis. This study reports the browning effects of rosiglitazone during the differentiation of iMSCs into adipocytes in association with the activation of MAPK and PI3K signaling pathways.

Aquaglyceroporins Are Differentially Expressed in Beige and White Adipocytes

“…Insulin, dexamethasone, rosiglitazone, and IBMX are commonly used to differentiate 3T3-L1 preadipocytes in white adipocytic cells. Although rosiglitazone has been reported to have browning effects during the adipocyte by activating MAPK and PI3K signalling pathways [38], it has also been extensively reported as an enhancer of white adipocyte full differentiation since it triggers peroxisome proliferator activator receptor gamma (PPARγ) overexpression, the master regulator of both BAT and WAT adipogenesis [39,40]. Adding factors that target β-adrenergic stimulation, such as L-rhamnose, T3, irisin, fibroblast growth factor 21, or follistatin to the previous cocktail have been described to induce fat browning [32,[41][42][43][44].…”

Usefulness of Mesenchymal Cell Lines for Bone and Cartilage Regeneration Research

“…Positive for ARS, APS, and Runx2 upregulation [71] Positive for ABS, TBS, and GAG assay in pellet culture [72]; low chondrogenic potential but stimulation of chondrocyte differentiation Positive for OROS, adipogenesis-related genes upregulation [71,73], and NRS [73] BMA13H Positive for ARS (reduced compared with primary cells) [74] Positive for ABS and GAG assay in 2D culture [74]; also positive for TBS, PSR and aggrecan and ColII immunostaining in 3D culture [75]; chondrogenic potential reduced compared with primary cells [74] Positive for OROS (reduced compared with primary cells) [74] SCP-1…”

<p>Reduced Beige Adipogenic Potential in Subcutaneous Adipocytes Derived from Obese Chinese Individuals</p>

“…Rosiglitazone is a potent PPARγ agonist that causes mitochondrial biogenesis and increased expression of several mitochondrial proteins. 26 The adipocyte expression of PPARγ in obesity was lower than normal-weight ones in the present study, which may contribute partly to the decreased beige inducible potential when facing BAinduction treatment in obesity.…”