Constitutively active Stat5A and Stat5B promote adipogenesis

Abstract

Objective The metabolic syndrome is an important social problem affecting many people in developed countries. Obesity is a leading cause of this syndrome, hence understanding molecular mechanisms underlying obesity is of prime importance for preventive medicine to develop novel methods to alleviate the corresponding social cost as well as for pharmaceutical companies to develop antimetabolic drugs. Methods Since adipocytes play an important role in obesity, we explored the signaling pathways leading to differentiation of adipocytes. We used a preadipocyte cell line to monitor the differentiation of adipocytes, and virusmediated gene transfer to assess the role of the transcription factor Stat5 in adipogenesis. Adipocyte differentiation was assessed by Northern blot and Western blot analyses as well as accumulation of fat droplets in cells. Promoter activity of the proadipogenic transcription factor peroxisome proliferator-activated receptor-gamma (PPARc) was evaluated by luciferase assay. Results Virus-mediated gene transfer of the constitutively active form of both Stat5A and Stat5B resulted in enhanced adipocyte differentiation in the absence of fetal bovine serum (FBS) as judged by expression of proadipogenic factors as well as accumulation of fat droplets in cells.Such a proadipogenic effect of Stat5 is, in part, mediated by its ability to enhance transcription of PPARc, a master transcriptional regulator in adipogenesis. Conclusion The constitutively active form of Stat5A and Stat5B promoted adipocyte differentiation in the absence of FBS via induction of PPARc.

The JAK-STAT Transcriptional Regulator, STAT-5, Activates the ATM DNA Damage Pathway to Induce HPV 31 Genome Amplification upon Epithelial Differentiation

“…A recent study suggested that the nuclear peroxisome proliferator-activated receptor γ (PPARγ) could activate CHK2 in the development of follicular thyroid cancer [24]. In addition, PPARγ transcription has been shown to be regulated by STAT-5 in adipogenesis [25]. We therefore investigated if the expression of PPARγ was altered by STAT-5 in HPV31-positive CIN612 cells.…”

The role of JAK–STAT signaling in adipose tissue function

“…This is supported by data showing that STAT5 can directly bind and transactivate the PPARγ promoter [39,55,100]. Many transcription factors have profound effects on adipocyte development, but PPARγ is a critical transcriptional regulator that is absolutely required for fat cell differentiation [6,61].…”

MDM2 facilitates adipocyte differentiation through CRTC-mediated activation of STAT3

“…Of the seven known STATs, only STAT3 and STAT5 are reported to positively affect adipogenesis. 3, 4, 5, 6, 7 Similarly, CREB has also been shown to enhance adipocyte differentiation. 8, 9, 10 Interestingly, although a dominant-negative CREB prevents induction of Cebpb during differentiation, a constitutive active CREB restores adipogenesis in cells with knockdown of C/EBP β , suggesting that CREB facilitates adipose conversion through others means than C/EBP β .…”